Alveolar Soft Part Sarcoma

Cancer MONDO:0011655 Pathograph 9 soft tissue sarcoma

Alveolar soft part sarcoma is a rare translocation-driven soft tissue sarcoma that most often affects adolescents and young adults. It commonly arises as a deep soft tissue mass of the extremities and is characterized by an ASPSCR1-TFE3 fusion, strong angiogenic biology, and a tendency toward delayed pulmonary and brain metastases.

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5
Pathophys.
1
Histopath.
5
Phenotypes
9
Pathograph
2
Genes
5
Treatments
3
Trials
1
Deep Research
⚙

Pathophysiology

5
ASPSCR1-TFE3 Fusion Oncogene
A characteristic unbalanced der(17)t(X;17)(p11;q25) translocation fuses ASPSCR1 to TFE3, creating an aberrant transcription factor that redirects gene expression programs in tumor cells.
mesenchymal cell link
ASPSCR1 link TFE3 link
positive regulation of transcription by RNA polymerase II link ⚠ ABNORMAL
Downstream
Angiogenic Tumor Program Aberrant transcriptional activity promotes angiogenic tumor biology
Mitochondrial Biology Program ASPSCR1-TFE3 transcriptional programs include mitochondrial biology.
Cyclin D1-CDK4 Cell-Cycle Dependency ASPSCR1-TFE3 transcriptional programs drive cyclin D1/CDK4-dependent proliferation
Show evidence (2 references)
PMID:37626447 SUPPORT Human Clinical
"The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion."
The review abstract directly supports the recurrent translocation and ASPSCR1-TFE3 fusion as defining disease biology.
PMID:38657118 SUPPORT In Vitro
"Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion."
The mechanistic study abstract supports ASPSCR1::TFE3 as the oncogenic driver fusion.
Angiogenic Tumor Program
Alveolar soft part sarcoma is typically highly vascular, with expression of angiogenic programs that support tumor growth and provide the rationale for antiangiogenic systemic therapies.
endothelial cell link
angiogenesis link ↑ INCREASED
Downstream
Metastatic Progression Vascular tumor biology contributes to hematogenous metastatic spread
Show evidence (2 references)
PMID:38657118 SUPPORT In Vitro
"identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology."
The mechanistic study directly links ASPSCR1::TFE3 to angiogenesis and cell-proliferation transcriptional programs.
PMID:37987424 SUPPORT Human Clinical
"Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3)."
The imaging cohort supports the highly vascular tumor phenotype in patients.
Mitochondrial Biology Program
ASPSCR1-TFE3 regulates mitochondrial biology and mitochondrial biogenesis as part of the core oncogenic transcriptional program.
mitochondrion organization link ⚠ ABNORMAL
Show evidence (2 references)
PMID:38657118 SUPPORT In Vitro
"identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology."
The mechanistic study identifies mitochondrial biology as a core ASPSCR1::TFE3 transcriptional program.
PMID:38657118 SUPPORT In Vitro
"The ASPSCR1::TFE3 fusion propels the growth of alveolar soft part sarcoma by activating transcriptional programs that regulate proliferation, angiogenesis, mitochondrial biogenesis, and differentiation and can be therapeutically targeted to improve treatment."
The paper's significance statement supports mitochondrial biogenesis as an activated ASPS transcriptional program.
Cyclin D1-CDK4 Cell-Cycle Dependency
Recent preclinical work shows that ASPSCR1-TFE3-driven transcriptional programs create a cyclin D1/CDK4-dependent proliferation state that may be targetable with CDK4/6 inhibition, especially in combination with angiogenesis inhibition.
cell cycle G1/S phase transition link ↑ INCREASED cell population proliferation link ↑ INCREASED
Show evidence (2 references)
PMID:38657118 SUPPORT In Vitro
"cell proliferation was driven by high levels of cyclin D1 expression."
This directly supports cyclin D1 as a cell-cycle effector of ASPS proliferation.
PMID:38657118 SUPPORT Model Organism
"combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts."
The xenograft result supports combined CDK4/6 and angiogenesis inhibition as a preclinical therapeutic vulnerability.
Metastatic Progression
Alveolar soft part sarcoma often follows an indolent primary course but can metastasize to the lungs, brain, bone, and other sites, sometimes years after initial diagnosis.
cell population proliferation link ↑ INCREASED
Show evidence (2 references)
PMID:35971085 SUPPORT Human Clinical
"The national study confirmed a unique feature of ASPS with frequent metastasis to the lung and brain but an indolent clinical course."
Population registry data support the combination of indolent course and frequent lung/brain metastasis.
PMID:40171452 SUPPORT Human Clinical
"Alveolar soft part sarcoma (ASPS) is a rare, indolent soft tissue sarcoma, with a high predilection for systemic dissemination."
A real-world clinical cohort supports the systemic dissemination tendency.
✶

Histopathology

1
Alveolar Soft Part Sarcoma Histology
Tumors have nests or organoid groups of polygonal cells separated by delicate vasculature, producing the classic alveolar pattern, and usually show nuclear TFE3 immunoreactivity.
Show evidence (1 reference)
PMID:38291475 SUPPORT Human Clinical
"ASPS had a characteristic pathological morphology. Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients."
The pathology cohort supports characteristic morphology plus TFE3 protein and rearrangement findings.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Alveolar Soft Part Sarcoma Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

5
Neoplasm 3
Deep Soft Tissue Mass Soft tissue neoplasm (HP:0031459)
Show evidence (2 references)
PMID:38291475 SUPPORT Human Clinical
"The clinical symptoms mainly included painless enlarged masses in deep soft tissues."
The clinicopathologic cohort directly supports a painless deep soft tissue mass presentation.
PMID:37987424 SUPPORT Human Clinical
"all tumors were deeply seated."
The imaging cohort supports the deep location and large mass-like presentation.
Hypervascular Tumor Imaging Pattern Soft tissue neoplasm (HP:0031459)
Show evidence (1 reference)
PMID:37987424 SUPPORT Human Clinical
"US revealed a well-defined heterogeneous hypoechoic pattern, with abundant flow signals in all patients (7/7)."
The imaging cohort supports abundant vascular flow as a characteristic clinical imaging phenotype.
Pulmonary Metastases Neoplasm of the lung (HP:0100526)
Show evidence (2 references)
PMID:35971085 SUPPORT Human Clinical
"adjuvant chemotherapy or radiotherapy did not affect survival, and 13 patients (45%) developed distant metastases in the lung (n = 12, 92%) and brain (n = 2, 15%)."
The national registry cohort directly supports lung metastasis during the disease course after localized ASPS.
PMID:40171452 SUPPORT Human Clinical
"The most common site of primary was the extremities (73%), and the most common sites of metastasis included the lungs (82%) and bones (21%)."
A contemporary real-world cohort also identifies lung as the most common metastatic site.
Other 2
Brain Metastases Neoplasm of the central nervous system (HP:0100006)
Show evidence (2 references)
PMID:40171452 SUPPORT Human Clinical
"Brain metastasis was seen in 7 patients at baseline (25.9%)."
The real-world cohort supports brain metastasis as a notable ASPS complication.
PMID:40171452 SUPPORT Human Clinical
"Patients with brain metastasis were seen to have markedly poor outcomes."
The same cohort supports clinical severity of brain metastasis in ASPS.
Bone Metastases Neoplasm of the skeletal system (HP:0010622)
Show evidence (2 references)
PMID:35971085 SUPPORT Human Clinical
"bone, n = 12"
The national registry cohort reports bone metastases in 14% of metastatic ASPS patients.
PMID:40171452 SUPPORT Human Clinical
"The most common site of primary was the extremities (73%), and the most common sites of metastasis included the lungs (82%) and bones (21%)."
A contemporary real-world cohort reports bones as a common metastatic site.
🧬

Genetic Associations

2
ASPSCR1-TFE3 Fusion - ASPSCR1 Partner
Show evidence (1 reference)
PMID:37626447 SUPPORT Human Clinical
"The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion."
The review abstract directly names ASPSCR1 as one partner in the defining ASPS fusion.
ASPSCR1-TFE3 Fusion - TFE3 Partner
Show evidence (1 reference)
PMID:37626447 SUPPORT Human Clinical
"The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion."
The review abstract directly names TFE3 as one partner in the defining ASPS fusion.
💊

Treatments

5
Complete Surgical Resection
Action: surgical excision MAXO:0000447
Complete resection with negative margins is the preferred local therapy when disease is localized and technically resectable.
Show evidence (1 reference)
PMID:37626447 SUPPORT Human Clinical
"Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours."
The review abstract directly supports complete surgical resection as the standard local treatment strategy.
Radiation Therapy
Action: radiation therapy MAXO:0000014
Radiation therapy can be used when surgical margins are inadequate or when tumors are unresectable.
Show evidence (1 reference)
PMID:37626447 SUPPORT Human Clinical
"Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours."
The same review abstract supports radiation therapy for inadequate margins or unresectable disease.
Antiangiogenic Targeted Therapy
Action: Pharmacotherapy NCIT:C15986
Agent: pazopanib ↗ sunitinib ↗
Antiangiogenic tyrosine kinase inhibitors, including pazopanib and sunitinib, are used for advanced ASPS and align with the tumor's angiogenic transcriptional program.
Mechanism Target:
INHIBITS Angiogenic Tumor Program — Antiangiogenic kinase inhibitors target vascular signaling that supports tumor growth.
Show evidence (2 references)
PMID:37626447 SUPPORT Human Clinical
"Although alveolar soft part sarcoma is refractory to conventional doxorubicin-based chemotherapy, monotherapy or combination therapy using tyrosine kinase inhibitors and immune checkpoint inhibitors have provided antitumor activity and emerged as new treatment strategies."
The review abstract supports tyrosine kinase inhibitors as an active systemic treatment class in ASPS.
PMID:35971085 SUPPORT Human Clinical
"Prolonged survival was seen in patients who received pazopanib treatment (p = 0.045), but not in those who received doxorubicin-based cytotoxic chemotherapy."
Registry data support pazopanib-associated prolonged survival in metastatic ASPS.
Atezolizumab
Action: Pharmacotherapy NCIT:C15986
Agent: Atezolizumab ↗
Anti-PD-L1 immune checkpoint inhibitor pharmacotherapy is an important systemic option for advanced ASPS, with prospective evidence for atezolizumab.
Show evidence (2 references)
PMID:37672694 SUPPORT Human Clinical
"An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses."
The prospective phase 2 study supports atezolizumab activity in advanced ASPS.
PMID:37672694 SUPPORT Human Clinical
"Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS."
The study conclusion supports immune checkpoint blockade as an effective systemic option in a subset of advanced ASPS patients.
Investigational CDK4/6 Inhibition
Action: Pharmacotherapy NCIT:C15986
Agent: palbociclib ↗
Palbociclib-sensitive cyclin D1/CDK4 dependence is supported preclinically and may provide a future strategy, particularly with antiangiogenic combinations; clinical translation remains investigational.
Mechanism Target:
INHIBITS Cyclin D1-CDK4 Cell-Cycle Dependency — Palbociclib inhibits CDK4/6-dependent tumor-cell proliferation.
Show evidence (1 reference)
PMID:38657118 PARTIAL Model Organism
"combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts."
This supports a preclinical, not yet established clinical, therapeutic rationale for CDK4/6 inhibition in ASPS.
🔬

Biochemical Markers

1
TFE3 Nuclear Immunoreactivity
Show evidence (1 reference)
PMID:38291475 SUPPORT Human Clinical
"Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients."
The clinicopathologic cohort directly supports TFE3 protein positivity and rearrangement testing as diagnostic features.
🔬

Clinical Trials

3
NCT03141684 PHASE_II
Phase 2 trial of atezolizumab alone or atezolizumab plus bevacizumab for advanced unresectable ASPS.
Show evidence (1 reference)
clinicaltrials:NCT03141684 SUPPORT Human Clinical
"This phase II trial studies how well atezolizumab or atezolizumab plus bevacizumab works in treating patients with alveolar soft part sarcoma that has not been treated, has spread from where it started to other places in the body (advanced) and cannot be removed by surgery (unresectable)."
ClinicalTrials.gov directly supports the atezolizumab plus/minus bevacizumab trial in advanced unresectable ASPS.
NCT02636725 PHASE_II
Phase 2 trial of combined axitinib and pembrolizumab in advanced ASPS and other soft tissue sarcomas.
Show evidence (1 reference)
clinicaltrials:NCT02636725 SUPPORT Human Clinical
"The purpose of this research study is to test if Axitinib together with Pembrolizumab can slow tumor growth and know the side effects of the combination treatment."
ClinicalTrials.gov directly supports investigation of combined axitinib and pembrolizumab.
NCT01391962 PHASE_II
Randomized phase 2 trial of cediranib versus sunitinib monotherapy with crossover at progression in metastatic ASPS.
Show evidence (1 reference)
clinicaltrials:NCT01391962 SUPPORT Human Clinical
"Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS."
ClinicalTrials.gov directly supports this VEGFR TKI comparison trial in advanced ASPS.
{ }

Source YAML

click to show 
name: Alveolar Soft Part Sarcoma
creation_date: "2026-05-09T14:04:43Z"
updated_date: "2026-05-09T22:33:12Z"
category: Cancer
categories:
- Sarcoma
- Soft Tissue Sarcoma
- Rare Cancer
parents:
- soft tissue sarcoma
disease_term:
  preferred_term: alveolar soft part sarcoma
  term:
    id: MONDO:0011655
    label: alveolar soft part sarcoma
description: >-
  Alveolar soft part sarcoma is a rare translocation-driven soft tissue sarcoma
  that most often affects adolescents and young adults. It commonly arises as a
  deep soft tissue mass of the extremities and is characterized by an
  ASPSCR1-TFE3 fusion, strong angiogenic biology, and a tendency toward delayed
  pulmonary and brain metastases.
synonyms:
- ASPS
- alveolar soft-part sarcoma
- alveolar soft tissue sarcoma
pathophysiology:
- name: ASPSCR1-TFE3 Fusion Oncogene
  description: >-
    A characteristic unbalanced der(17)t(X;17)(p11;q25) translocation fuses
    ASPSCR1 to TFE3, creating an aberrant transcription factor that redirects
    gene expression programs in tumor cells.
  genes:
  - preferred_term: ASPSCR1
    term:
      id: hgnc:13825
      label: ASPSCR1
  - preferred_term: TFE3
    term:
      id: hgnc:11752
      label: TFE3
  cell_types:
  - preferred_term: mesenchymal cell
    term:
      id: CL:0008019
      label: mesenchymal cell
  biological_processes:
  - preferred_term: positive regulation of transcription by RNA polymerase II
    modifier: ABNORMAL
    term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The neoplasm is characterized by a specific chromosomal translocation,
      der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion.
    explanation: >-
      The review abstract directly supports the recurrent translocation and
      ASPSCR1-TFE3 fusion as defining disease biology.
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven
      by the ASPSCR1::TFE3 fusion.
    explanation: >-
      The mechanistic study abstract supports ASPSCR1::TFE3 as the oncogenic
      driver fusion.
  downstream:
  - target: Angiogenic Tumor Program
    description: Aberrant transcriptional activity promotes angiogenic tumor biology
  - target: Mitochondrial Biology Program
    description: ASPSCR1-TFE3 transcriptional programs include mitochondrial biology.
  - target: Cyclin D1-CDK4 Cell-Cycle Dependency
    description: ASPSCR1-TFE3 transcriptional programs drive cyclin D1/CDK4-dependent proliferation
- name: Angiogenic Tumor Program
  description: >-
    Alveolar soft part sarcoma is typically highly vascular, with expression of
    angiogenic programs that support tumor growth and provide the rationale for
    antiangiogenic systemic therapies.
  cell_types:
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  biological_processes:
  - preferred_term: angiogenesis
    modifier: INCREASED
    term:
      id: GO:0001525
      label: angiogenesis
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      identifying the essential role of ASPSCR1::TFE3 in tumor cell viability
      by regulating core transcriptional programs involved in cell
      proliferation, angiogenesis, and mitochondrial biology.
    explanation: >-
      The mechanistic study directly links ASPSCR1::TFE3 to angiogenesis and
      cell-proliferation transcriptional programs.
  - reference: PMID:37987424
    reference_title: "Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Large peritumoral feeding vessels were systematically found and identified
      on ultrasonography (7/7), MRI (10/10), and CT (3/3).
    explanation: >-
      The imaging cohort supports the highly vascular tumor phenotype in
      patients.
  downstream:
  - target: Metastatic Progression
    description: Vascular tumor biology contributes to hematogenous metastatic spread
- name: Mitochondrial Biology Program
  description: >-
    ASPSCR1-TFE3 regulates mitochondrial biology and mitochondrial biogenesis as
    part of the core oncogenic transcriptional program.
  biological_processes:
  - preferred_term: mitochondrion organization
    modifier: ABNORMAL
    term:
      id: GO:0007005
      label: mitochondrion organization
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by
      regulating core transcriptional programs involved in cell proliferation,
      angiogenesis, and mitochondrial biology.
    explanation: >-
      The mechanistic study identifies mitochondrial biology as a core
      ASPSCR1::TFE3 transcriptional program.
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The ASPSCR1::TFE3 fusion propels the growth of alveolar soft part sarcoma
      by activating transcriptional programs that regulate proliferation,
      angiogenesis, mitochondrial biogenesis, and differentiation and can be
      therapeutically targeted to improve treatment.
    explanation: >-
      The paper's significance statement supports mitochondrial biogenesis as an
      activated ASPS transcriptional program.
- name: Cyclin D1-CDK4 Cell-Cycle Dependency
  description: >-
    Recent preclinical work shows that ASPSCR1-TFE3-driven transcriptional
    programs create a cyclin D1/CDK4-dependent proliferation state that may be
    targetable with CDK4/6 inhibition, especially in combination with
    angiogenesis inhibition.
  biological_processes:
  - preferred_term: cell cycle G1/S phase transition
    modifier: INCREASED
    term:
      id: GO:0044843
      label: cell cycle G1/S phase transition
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      cell proliferation was driven by high levels of cyclin D1 expression.
    explanation: >-
      This directly supports cyclin D1 as a cell-cycle effector of ASPS
      proliferation.
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      combined inhibition of CDK4/6 and angiogenesis halted tumor growth in
      xenografts.
    explanation: >-
      The xenograft result supports combined CDK4/6 and angiogenesis inhibition
      as a preclinical therapeutic vulnerability.
- name: Metastatic Progression
  description: >-
    Alveolar soft part sarcoma often follows an indolent primary course but can
    metastasize to the lungs, brain, bone, and other sites, sometimes years
    after initial diagnosis.
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  evidence:
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The national study confirmed a unique feature of ASPS with frequent
      metastasis to the lung and brain but an indolent clinical course.
    explanation: >-
      Population registry data support the combination of indolent course and
      frequent lung/brain metastasis.
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Alveolar soft part sarcoma (ASPS) is a rare, indolent soft tissue
      sarcoma, with a high predilection for systemic dissemination.
    explanation: >-
      A real-world clinical cohort supports the systemic dissemination
      tendency.
histopathology:
- name: Alveolar Soft Part Sarcoma Histology
  finding_term:
    preferred_term: Alveolar Soft Part Sarcoma
    term:
      id: NCIT:C3750
      label: Alveolar Soft Part Sarcoma
  diagnostic: true
  description: >-
    Tumors have nests or organoid groups of polygonal cells separated by
    delicate vasculature, producing the classic alveolar pattern, and usually
    show nuclear TFE3 immunoreactivity.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ASPS had a characteristic pathological morphology. Twenty-four patients
      were positive for TFE3, and TFE3 gene rearrangement was detected in 12
      patients.
    explanation: >-
      The pathology cohort supports characteristic morphology plus TFE3 protein
      and rearrangement findings.
phenotypes:
- category: Musculoskeletal
  name: Deep Soft Tissue Mass
  diagnostic: true
  description: >-
    Patients commonly present with a slow-growing deep soft tissue mass,
    especially in the extremities.
  phenotype_term:
    preferred_term: Deep soft tissue mass
    term:
      id: HP:0031459
      label: Soft tissue neoplasm
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical symptoms mainly included painless enlarged masses in deep
      soft tissues.
    explanation: >-
      The clinicopathologic cohort directly supports a painless deep soft
      tissue mass presentation.
  - reference: PMID:37987424
    reference_title: "Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      all tumors were deeply seated.
    explanation: >-
      The imaging cohort supports the deep location and large mass-like
      presentation.
- category: Vascular
  name: Hypervascular Tumor Imaging Pattern
  description: >-
    Imaging often shows abundant internal vascularity, flow voids, and large
    peritumoral feeding vessels, which can make ASPS resemble a vascular lesion.
  phenotype_term:
    preferred_term: hypervascular soft tissue neoplasm
    term:
      id: HP:0031459
      label: Soft tissue neoplasm
  evidence:
  - reference: PMID:37987424
    reference_title: "Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      US revealed a well-defined heterogeneous hypoechoic pattern, with abundant
      flow signals in all patients (7/7).
    explanation: >-
      The imaging cohort supports abundant vascular flow as a characteristic
      clinical imaging phenotype.
- category: Respiratory
  name: Pulmonary Metastases
  description: >-
    Hematogenous spread commonly involves the lung and may be present at
    diagnosis or emerge after a long interval.
  phenotype_term:
    preferred_term: Neoplasm of the lung
    term:
      id: HP:0100526
      label: Neoplasm of the lung
  evidence:
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      adjuvant chemotherapy or radiotherapy did not affect survival, and 13
      patients (45%) developed distant metastases in the lung (n = 12, 92%) and
      brain (n = 2, 15%).
    explanation: >-
      The national registry cohort directly supports lung metastasis during the
      disease course after localized ASPS.
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most common site of primary was the extremities (73%), and the most
      common sites of metastasis included the lungs (82%) and bones (21%).
    explanation: >-
      A contemporary real-world cohort also identifies lung as the most common
      metastatic site.
- category: Neurologic
  name: Brain Metastases
  description: >-
    Brain metastases are a recognized complication in advanced disease.
  phenotype_term:
    preferred_term: Neoplasm of the central nervous system
    term:
      id: HP:0100006
      label: Neoplasm of the central nervous system
  evidence:
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Brain metastasis was seen in 7 patients at baseline (25.9%).
    explanation: >-
      The real-world cohort supports brain metastasis as a notable ASPS
      complication.
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients with brain metastasis were seen to have markedly poor outcomes.
    explanation: >-
      The same cohort supports clinical severity of brain metastasis in ASPS.
- category: Musculoskeletal
  name: Bone Metastases
  description: >-
    Bone is a recurrent metastatic site in advanced alveolar soft part sarcoma.
  phenotype_term:
    preferred_term: Bone metastases
    term:
      id: HP:0010622
      label: Neoplasm of the skeletal system
  evidence:
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      bone, n = 12
    explanation: >-
      The national registry cohort reports bone metastases in 14% of metastatic
      ASPS patients.
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most common site of primary was the extremities (73%), and the most
      common sites of metastasis included the lungs (82%) and bones (21%).
    explanation: >-
      A contemporary real-world cohort reports bones as a common metastatic site.
biochemical:
- name: TFE3 Nuclear Immunoreactivity
  notes: >-
    Nuclear TFE3 immunohistochemistry can support the diagnosis when integrated
    with morphology and molecular confirmation of the ASPSCR1-TFE3 fusion.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement
      was detected in 12 patients.
    explanation: >-
      The clinicopathologic cohort directly supports TFE3 protein positivity
      and rearrangement testing as diagnostic features.
genetic:
- name: ASPSCR1-TFE3 Fusion - ASPSCR1 Partner
  gene_term:
    preferred_term: ASPSCR1
    term:
      id: hgnc:13825
      label: ASPSCR1
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  notes: >-
    ASPSCR1 is one partner in the recurrent somatic ASPSCR1-TFE3 fusion that
    defines alveolar soft part sarcoma.
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The neoplasm is characterized by a specific chromosomal translocation,
      der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion.
    explanation: >-
      The review abstract directly names ASPSCR1 as one partner in the defining
      ASPS fusion.
- name: ASPSCR1-TFE3 Fusion - TFE3 Partner
  gene_term:
    preferred_term: TFE3
    term:
      id: hgnc:11752
      label: TFE3
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  notes: >-
    TFE3 is the transcription-factor partner in the recurrent somatic
    ASPSCR1-TFE3 fusion.
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The neoplasm is characterized by a specific chromosomal translocation,
      der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion.
    explanation: >-
      The review abstract directly names TFE3 as one partner in the defining
      ASPS fusion.
treatments:
- name: Complete Surgical Resection
  description: >-
    Complete resection with negative margins is the preferred local therapy
    when disease is localized and technically resectable.
  treatment_term:
    preferred_term: surgical excision
    term:
      id: MAXO:0000447
      label: surgical excision
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Complete surgical resection remains the standard treatment strategy,
      whereas radiotherapy is indicated for patients with inadequate surgical
      margins or unresectable tumours.
    explanation: >-
      The review abstract directly supports complete surgical resection as the
      standard local treatment strategy.
- name: Radiation Therapy
  description: >-
    Radiation therapy can be used when surgical margins are inadequate or when
    tumors are unresectable.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Complete surgical resection remains the standard treatment strategy,
      whereas radiotherapy is indicated for patients with inadequate surgical
      margins or unresectable tumours.
    explanation: >-
      The same review abstract supports radiation therapy for inadequate
      margins or unresectable disease.
- name: Antiangiogenic Targeted Therapy
  description: >-
    Antiangiogenic tyrosine kinase inhibitors, including pazopanib and
    sunitinib, are used for advanced ASPS and align with the tumor's angiogenic
    transcriptional program.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: pazopanib
      term:
        id: CHEBI:71219
        label: pazopanib
    - preferred_term: sunitinib
      term:
        id: CHEBI:38940
        label: sunitinib
  target_mechanisms:
  - target: Angiogenic Tumor Program
    treatment_effect: INHIBITS
    description: Antiangiogenic kinase inhibitors target vascular signaling that supports tumor growth.
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Although alveolar soft part sarcoma is refractory to conventional
      doxorubicin-based chemotherapy, monotherapy or combination therapy using
      tyrosine kinase inhibitors and immune checkpoint inhibitors have provided
      antitumor activity and emerged as new treatment strategies.
    explanation: >-
      The review abstract supports tyrosine kinase inhibitors as an active
      systemic treatment class in ASPS.
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Prolonged survival was seen in patients who received pazopanib treatment
      (p = 0.045), but not in those who received doxorubicin-based cytotoxic
      chemotherapy.
    explanation: >-
      Registry data support pazopanib-associated prolonged survival in
      metastatic ASPS.
- name: Atezolizumab
  description: >-
    Anti-PD-L1 immune checkpoint inhibitor pharmacotherapy is an important
    systemic option for advanced ASPS, with prospective evidence for
    atezolizumab.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: Atezolizumab
      term:
        id: NCIT:C106250
        label: Atezolizumab
  evidence:
  - reference: PMID:37672694
    reference_title: "Atezolizumab for Advanced Alveolar Soft Part Sarcoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      An objective response was observed in 19 of 52 patients (37%), with 1
      complete response and 18 partial responses.
    explanation: >-
      The prospective phase 2 study supports atezolizumab activity in advanced
      ASPS.
  - reference: PMID:37672694
    reference_title: "Atezolizumab for Advanced Alveolar Soft Part Sarcoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Atezolizumab was effective at inducing sustained responses in
      approximately one third of patients with advanced ASPS.
    explanation: >-
      The study conclusion supports immune checkpoint blockade as an effective
      systemic option in a subset of advanced ASPS patients.
- name: Investigational CDK4/6 Inhibition
  description: >-
    Palbociclib-sensitive cyclin D1/CDK4 dependence is supported preclinically
    and may provide a future strategy, particularly with antiangiogenic
    combinations; clinical translation remains investigational.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: palbociclib
      term:
        id: CHEBI:85993
        label: palbociclib
  target_mechanisms:
  - target: Cyclin D1-CDK4 Cell-Cycle Dependency
    treatment_effect: INHIBITS
    description: Palbociclib inhibits CDK4/6-dependent tumor-cell proliferation.
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: PARTIAL
    evidence_source: MODEL_ORGANISM
    snippet: >-
      combined inhibition of CDK4/6 and angiogenesis halted tumor growth in
      xenografts.
    explanation: >-
      This supports a preclinical, not yet established clinical, therapeutic
      rationale for CDK4/6 inhibition in ASPS.
diagnosis:
- name: Molecular Fusion Testing
  description: >-
    Diagnosis combines morphology, TFE3 immunohistochemistry, and molecular
    confirmation of ASPSCR1-TFE3 rearrangement by FISH, RT-PCR, or sequencing.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      ASPS has character TFE3 protein and gene expression, and the diagnosis is
      relatively specific.
    explanation: >-
      The clinicopathologic cohort supports TFE3 protein and rearrangement
      findings as diagnostic features.
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The diagnosis requires comprehensive analysis of clinical history,
      histological morphology, and immunohistochemistry.
    explanation: >-
      This supports an integrated diagnostic approach rather than relying on a
      single test.
clinical_trials:
- name: NCT03141684
  phase: PHASE_II
  description: >-
    Phase 2 trial of atezolizumab alone or atezolizumab plus bevacizumab for
    advanced unresectable ASPS.
  evidence:
  - reference: clinicaltrials:NCT03141684
    reference_title: "A Phase 2 Study of Anti-PD-L1 Antibody (Atezolizumab) in Alveolar Soft Part Sarcoma"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This phase II trial studies how well atezolizumab or atezolizumab plus
      bevacizumab works in treating patients with alveolar soft part sarcoma
      that has not been treated, has spread from where it started to other
      places in the body (advanced) and cannot be removed by surgery
      (unresectable).
    explanation: >-
      ClinicalTrials.gov directly supports the atezolizumab plus/minus
      bevacizumab trial in advanced unresectable ASPS.
- name: NCT02636725
  phase: PHASE_II
  description: >-
    Phase 2 trial of combined axitinib and pembrolizumab in advanced ASPS and
    other soft tissue sarcomas.
  evidence:
  - reference: clinicaltrials:NCT02636725
    reference_title: "A Phase II Trial of Concurrent Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma (ASPS) and Other Soft Tissue Sarcomas (STS)"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The purpose of this research study is to test if Axitinib together with
      Pembrolizumab can slow tumor growth and know the side effects of the
      combination treatment.
    explanation: >-
      ClinicalTrials.gov directly supports investigation of combined axitinib
      and pembrolizumab.
- name: NCT01391962
  phase: PHASE_II
  description: >-
    Randomized phase 2 trial of cediranib versus sunitinib monotherapy with
    crossover at progression in metastatic ASPS.
  evidence:
  - reference: clinicaltrials:NCT01391962
    reference_title: "A Phase II Trial In Which Patients With Metastatic Alveolar Soft Part Sarcoma Are Randomized to Either Sunitinib or Cediranib Monotherapy, With Cross-Over at Disease Progression"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Determine the objective response rate (ORR) of single-agent cediranib and
      single-agent sunitinib malate in patients with advanced ASPS.
    explanation: >-
      ClinicalTrials.gov directly supports this VEGFR TKI comparison trial in
      advanced ASPS.
notes: >-
  Falcon deep research emphasized the ASPSCR1-TFE3 fusion, angiogenic tumor
  biology, high lung and brain metastatic burden, atezolizumab clinical
  activity, and emerging preclinical CDK4/6 vulnerability. Report citations
  were mapped to PMID-backed caches where possible before YAML evidence was
  added.
📚

References & Deep Research

Deep Research

1
Falcon ▸
Disease Characteristics Research Template
Edison Scientific Literature 28 citations 2026-05-09T10:32:00.013707

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Alveolar Soft Part Sarcoma
  • MONDO ID: (if available)
  • Category: Cancer

Research Objectives

Please provide a comprehensive research report on Alveolar Soft Part Sarcoma covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
  • Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Alveolar Soft Part Sarcoma (ASPS): Disease Characteristics Research Report (2026-05-09)

Executive summary

Alveolar soft part sarcoma (ASPS) is an ultra-rare, translocation-defined soft-tissue sarcoma driven by the ASPSCR1::TFE3 fusion that typically presents as a slow-growing, deeply located soft-tissue mass in adolescents and young adults, but with a high propensity for early or eventual metastasis—most commonly to lung, bone, and brain. Recent practice-changing progress includes durable responses to immune checkpoint blockade, notably atezolizumab, with an objective response rate (ORR) of 37% and median progression-free survival (PFS) of 20.8 months in a 2023 phase 2 study that underpinned regulatory approval. Concurrently, mechanistic 2024 work has clarified fusion-driven transcriptional programs and identified targetable dependencies (Cyclin D1/CDK4) that rationalize combination strategies with anti-angiogenic therapy.

Evidence summary table

The following table consolidates disease identity, clinicopathology, diagnostics, imaging, molecular biology, and the most recent outcome statistics extracted from the tool-retrieved evidence.

Domain Item Key details / quantitative values Evidence
Disease identity Definition Ultra-rare, translocation-defined soft-tissue sarcoma characterized by der(17)t(X;17)(p11.2;q25) creating the ASPSCR1::TFE3 fusion; typically indolent but highly metastatic and often vascular. Incidence reported as ~1 per 10 million population/year and 0.2–0.9% of soft-tissue sarcomas. (fujiwara2023advancesintreatment pages 1-2)
Disease identity Preferred name / synonym Alveolar soft part sarcoma (ASPS); literature also refers to alveolar soft-part sarcoma. Fusion historically described as ASPL-TFE3 / TFE3-ASPL in older literature. (fujiwara2023advancesintreatment pages 1-2, fernandes2024realworldoutcomes pages 1-2)
Disease identity Identifiers available from retrieved evidence Retrieved evidence supports disease name and molecular definition, but MONDO, Orphanet, ICD-10/ICD-11, MeSH, and OMIM identifiers were not directly retrieved in the gathered evidence set; these should be added from ontology resources separately. (fujiwara2023advancesintreatment pages 1-2)
Clinicopathology Age distribution Peak age 15–35 years; SEER-based review reports median age 25 years, 72% <30 years. Recent cohorts: mean 27.1 ± 10.7 y (Spinnato 2023, n=12), median 27.5 y (Zhang 2024, n=26), median 28 y (Fernandes 2024, n=34). (fujiwara2023advancesintreatment pages 1-2, spinnato2023imagingfeaturesof pages 1-2, zhang2024alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 1-2)
Clinicopathology Sex distribution Often slight female predominance: review reports 58% female and approximate male:female ratio ~1:1.5; however real-world 2024 Indian cohort showed slight male predominance (19 M / 15 F). (fujiwara2023advancesintreatment pages 1-2, cong2025recentprogressin pages 1-2, fernandes2024realworldoutcomes pages 1-2)
Clinicopathology Primary sites Most common sites: extremities 61%, trunk 20%, head/neck 9%, internal organs 8% in review data. In Fernandes 2024, 73% arose in extremities. Pediatric series showed 50% head/neck and 50% trunk/limbs. (fujiwara2023advancesintreatment pages 1-2, fernandes2024realworldoutcomes pages 1-2, wang2024ultrasoundcharacteristicsof pages 1-2)
Clinicopathology Typical presentation Usually a slow-growing, painless deep soft-tissue mass; tumors are often highly vascular. Zhang 2024: painless enlarged masses in deep soft tissue; Spinnato 2023: all tumors were deeply seated with mean longest diameter 7.6 ± 2.9 cm. (zhang2024alveolarsoftpart pages 1-2, spinnato2023imagingfeaturesof pages 1-2)
Clinicopathology Metastasis pattern Common metastatic sites are lung, bone, and brain. Japanese population study: metastatic cases had lung 99%, bone 14%, brain 11%; localized cases later developed distant metastases in 45%. Fernandes 2024: lung 82%, bone 21%, brain metastasis at baseline 25.9%. (fujiwara2022alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 1-2, fernandes2024realworldoutcomes pages 2-6)
Clinicopathology Metastasis at diagnosis High baseline dissemination: Spinnato 2023 8/12 (66.7%) metastatic at baseline; Fujiwara 2022 72% metastatic at presentation; Fernandes 2024 27/34 (79%) metastatic at presentation. Larger tumors were associated with metastasis in imaging cohorts. (spinnato2023imagingfeaturesof pages 1-2, fujiwara2022alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 2-6)
Diagnostics Histopathology Classic morphology: organoid/nested epithelioid cells with pseudoalveolar architecture, abundant eosinophilic cytoplasm, sinusoidal vasculature; PAS-positive diastase-resistant crystalline material may be present. (fujiwara2023advancesintreatment pages 1-2, zhang2024alveolarsoftpart pages 4-7)
Diagnostics PAS crystals / PAS positivity Review data describe PAS-positive glycogen and rod-shaped crystals as characteristic. In Zhang 2024, 20/26 tumors were PAS-positive. (fujiwara2023advancesintreatment pages 1-2, zhang2024alveolarsoftpart pages 4-7)
Diagnostics TFE3 immunohistochemistry Nuclear TFE3 staining is a major diagnostic hallmark. Zhang 2024: 24/26 (92.3%) TFE3-positive. Review literature describes sensitivity often >95%, but specificity is imperfect and false positives can occur. (zhang2024alveolarsoftpart pages 2-4, zhang2024alveolarsoftpart pages 4-7, cong2025recentprogressin pages 4-5)
Diagnostics Fusion event Pathognomonic chromosomal abnormality: der(17)t(X;17)(p11.2;q25) producing ASPSCR1::TFE3 fusion. This is the key molecular defining event in ASPS. (fujiwara2023advancesintreatment pages 1-2, fujiwara2022alveolarsoftpart pages 1-2, sicinska2024aspscr1tfe3drivesalveolar pages 1-3)
Diagnostics Fusion testing methods Molecular confirmation can be performed by FISH, RT-PCR, and increasingly RNA sequencing/NGS. Zhang 2024: 12/12 tested showed TFE3 rearrangement by FISH in the tested subset. (zhang2024alveolarsoftpart pages 2-4, cong2025recentprogressin pages 3-4, cong2025recentprogressin pages 4-5)
Imaging Characteristic imaging hallmarks MRI: slight/mild T1 hyperintensity, T2 hyperintensity, frequent flow voids, peritumoral edema; US: well-defined hypoechoic heterogeneous lesion with abundant Doppler flow; large peritumoral feeding vessels seen on US/MRI/CT. (spinnato2023imagingfeaturesof pages 1-2, spinnato2023imagingfeaturesof pages 8-10, spinnato2023imagingfeaturesof pages 2-4)
Imaging Imaging risk marker In Spinnato 2023, tumor size >5 cm was associated with metastasis at diagnosis (p=0.01), with OR 45.0 (95% CI 1.49–1358.36, p=0.0285). Pediatric US study found moderate correlation between size and metastasis risk (r=0.64). (spinnato2023imagingfeaturesof pages 1-2, wang2024ultrasoundcharacteristicsof pages 1-2)
Molecular pathogenesis Core biology ASPSCR1::TFE3 is essential for tumor cell viability and drives transcriptional programs in proliferation, angiogenesis, mitochondrial biology, and differentiation; it engages enhancer/promoter complexes and epigenetic regulators. (sicinska2024aspscr1tfe3drivesalveolar pages 1-3, sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 8-9)
Molecular pathogenesis Targetable downstream dependencies 2024 mechanistic work identified Cyclin D1/CDK4 dependence and showed palbociclib reduced proliferation; palbociclib + sunitinib was more effective than either alone in xenografts. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 13-14)
Treatment (recent) Atezolizumab phase 2 (NEJM 2023) Multicenter single-group phase 2; 52 evaluable patients. ORR 37% (19/52) = 1 CR + 18 PR; median time to response 3.6 mo; median duration of response 24.7 mo; median PFS 20.8 mo; no treatment-related grade 4/5 AEs. (chen2023atezolizumabforadvanced pages 1-3, chen2023atezolizumabforadvanced pages 5-7, chen2023atezolizumabforadvanced pages 7-8)
Treatment (recent) Atezolizumab regulatory relevance / implementation Study formed the basis for FDA approval of atezolizumab for advanced ASPS in late 2022; ongoing trial platform continues as NCT03141684 (atezolizumab alone or with bevacizumab). (chen2023atezolizumabforadvanced pages 1-3, NCT03141684 chunk 2, NCT03141684 chunk 3)
Treatment (real-world) TKI outcomes in Fernandes 2024 In metastatic ASPS, 90% received first-line TKI. Median PFS 12 mo overall for first-line TKI monotherapy; sunitinib ORR 36%, disease-control rate 64%; median PFS numerically 15 vs 11 mo for sunitinib vs non-sunitinib TKIs. (fernandes2024realworldoutcomes pages 2-6, fernandes2024realworldoutcomes pages 6-8)
Treatment (real-world) ICI outcomes in Fernandes 2024 7 advanced-disease patients received ICIs (3 atezolizumab, 4 nivolumab). Atezolizumab produced prolonged disease control in some patients (progression-free at 20 and 15 months in cohort summary). Nivolumab included one ongoing complete metabolic response with duration ~52 months. (fernandes2024realworldoutcomes pages 1-2, fernandes2024realworldoutcomes pages 2-6, fernandes2024realworldoutcomes pages 6-8)
Prognosis Population survival (Fujiwara 2022) In 120 Japanese patients, 5-year disease-specific survival (DSS) 68% overall, 86% localized, 62% metastatic (p=0.019). Metastasis at presentation was the only adverse prognostic factor (HR 7.65, p=0.048). (fujiwara2022alveolarsoftpart pages 1-2)
Prognosis Additional cohort outcomes Fernandes 2024 metastatic cohort: median OS 36 mo, 3-year OS 52%; brain metastasis associated with poor survival (9.4 vs 56 mo, p=0.003). Zhang 2024: prognosis associated with sex (P=0.006), tumor size (P=0.031), and metastasis (P=0.043). (fernandes2024realworldoutcomes pages 2-6, zhang2024alveolarsoftpart pages 4-7, zhang2024alveolarsoftpart pages 2-4)
Trials / current implementation Active and landmark trial programs Key ASPS systemic-therapy trials include NCT03141684 (atezolizumab ± bevacizumab), NCT02636725 (axitinib + pembrolizumab), and NCT01391962 (randomized phase 2 cediranib vs sunitinib; actual enrollment 34). (NCT03141684 chunk 2, NCT02636725 chunk 2, NCT01391962 chunk 1)

Table: This table condenses the most actionable disease-level evidence for alveolar soft part sarcoma, including identity, clinicopathologic characteristics, diagnostic hallmarks, and the most important recent treatment and survival data. It is designed to support knowledge-base population with quantitative facts and direct evidence links.

1. Disease information

1.1 Definition and overview

ASPS is an ultra-rare soft-tissue sarcoma characterized by a specific chromosomal translocation der(17)t(X;17)(p11.2;q25) producing the ASPSCR1::TFE3 fusion, with an indolent primary tumor behavior but marked metastatic potential. A recent review describes ASPS as “a rare neoplasm of uncertain histogenesis… characterized by a specific chromosomal translocation… that results in ASPSCR1–TFE3 gene fusion,” and summarizes typical sites (extremities/trunk/head–neck) and metastatic predilection (lung/bone/brain). (fujiwara2023advancesintreatment pages 1-2)

1.2 Key identifiers (OMIM, Orphanet, ICD, MeSH, MONDO)

Within the tool-retrieved evidence set, formal ontology identifiers (OMIM, Orphanet/ORPHA, ICD-10/ICD-11, MeSH, MONDO) were not captured in full text and therefore cannot be asserted without external ontology lookup. The disease name and its defining fusion lesion were consistently supported in the retrieved primary literature and reviews. (fujiwara2023advancesintreatment pages 1-2)

1.3 Synonyms and alternative names

Common written variants include “alveolar soft part sarcoma” and “alveolar soft-part sarcoma.” The canonical fusion has also been described historically as “ASPL-TFE3” or “TFE3-ASPL” in older literature; recent papers use ASPSCR1::TFE3. (fujiwara2023advancesintreatment pages 1-2, fernandes2024realworldoutcomes pages 1-2)

1.4 Evidence source types

This report integrates aggregated evidence from population-based registries and retrospective cohorts (human clinical), prospective interventional trials (human clinical), and mechanistic preclinical models (in vitro, xenograft/PDX). (fujiwara2022alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 2-6, chen2023atezolizumabforadvanced pages 1-3, sicinska2024aspscr1tfe3drivesalveolar pages 14-16)

2. Etiology

2.1 Disease causal factors

Primary causal factor (genetic/driver lesion): The defining lesion is an unbalanced t(X;17)(p11.2;q25) producing ASPSCR1::TFE3, a chimeric transcription factor essential for tumor viability. (fujiwara2023advancesintreatment pages 1-2, fujiwara2022alveolarsoftpart pages 1-2, sicinska2024aspscr1tfe3drivesalveolar pages 1-3)

Mechanistic nature: ASPSCR1::TFE3 functions as an oncogenic transcriptional regulator that occupies active chromatin and coordinates programs including proliferation and angiogenesis. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 8-9)

2.2 Risk factors

No specific inherited predisposition, environmental exposure, or infectious agent risk factors were identified in the retrieved evidence. The most consistent “risk” correlates relate to clinical factors associated with metastatic presentation (e.g., tumor size, deep location, and age >25 years in a registry cohort) rather than causal exposures. (fujiwara2022alveolarsoftpart pages 1-2, spinnato2023imagingfeaturesof pages 1-2)

2.3 Protective factors / gene–environment interactions

No protective factors or gene–environment interactions were identified in the retrieved evidence set.

3. Phenotypes (clinical presentation)

3.1 Common phenotypes and suggested HPO terms

Deep soft-tissue mass; often painless, slow-growing - Evidence: “The clinical symptoms mainly included painless enlarged masses in deep soft tissues.” (Zhang 2024) (zhang2024alveolarsoftpart pages 1-2) - Suggested HPO: - Soft tissue neoplasm (HP:0002664) - Painless mass (HP:0031509) (term availability may vary)

High vascularity / prominent feeding vessels (imaging phenotype) - Evidence: ASPS lesions show abundant intratumoral/peritumoral vascularity with prominent feeding vessels on US/MRI/CT. (spinnato2023imagingfeaturesof pages 1-2, spinnato2023imagingfeaturesof pages 8-10) - Suggested HPO (proxy imaging/vascular): - Increased vascularity (phenotype representation may be recorded clinically rather than as a specific HPO term)

Metastatic disease manifestations - Lung metastasis (common): registry and cohort data show lung as the dominant metastatic site. (fujiwara2022alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 2-6) - Brain metastasis (notable in ASPS): baseline brain metastasis 25.9% in one real-world cohort with poor outcomes. (fernandes2024realworldoutcomes pages 2-6) - Suggested HPO: - Neoplasm metastasis (HP:0003002) - Pulmonary metastasis (HP:0031411) - Brain metastasis (HP:0007297)

3.2 Age of onset and progression

ASPS most commonly affects adolescents and young adults (peak ~15–35 years; SEER median age ~25; majority <30), and often follows an indolent course that can delay diagnosis, but with frequent metastasis at baseline or later. (fujiwara2023advancesintreatment pages 1-2, fujiwara2022alveolarsoftpart pages 1-2, spinnato2023imagingfeaturesof pages 1-2)

3.3 Frequency and severity

Quantitative frequencies vary by cohort and ascertainment, but baseline metastasis rates are often high: - 72% metastatic at presentation in a Japanese registry (n=120). (fujiwara2022alveolarsoftpart pages 1-2) - 66.7% metastatic at baseline in an imaging cohort (n=12). (spinnato2023imagingfeaturesof pages 1-2) - 79% metastatic at presentation in a tertiary-care real-world cohort (n=34). (fernandes2024realworldoutcomes pages 2-6)

3.4 Quality of life impact

QoL instruments (EQ-5D/SF-36) were not reported in the retrieved evidence. QoL impact is inferred from tumor burden and metastatic complications (notably CNS involvement) but cannot be quantified here.

4. Genetic / molecular information

4.1 Causal genes and chromosomal abnormalities

  • ASPSCR1 and TFE3 are implicated via the defining fusion ASPSCR1::TFE3 produced by der(17)t(X;17)(p11.2;q25). (fujiwara2023advancesintreatment pages 1-2, sicinska2024aspscr1tfe3drivesalveolar pages 1-3)

4.2 Pathogenic variants and variant properties

ASPS is primarily driven by a somatic structural variant (fusion/translocation) rather than recurrent point mutations in the retrieved sources. - Variant class: structural rearrangement (fusion) - Origin: somatic (tumor) - Detection: FISH/RT-PCR/RNA-seq/NGS (methods discussed in recent pathology sources). (zhang2024alveolarsoftpart pages 2-4, cong2025recentprogressin pages 4-5)

Population allele frequencies (gnomAD/ExAC) are not applicable for a tumor-specific fusion.

4.3 Diagnostic biomarker performance (TFE3)

TFE3 nuclear immunohistochemistry (IHC) is a key marker, but practical specificity can vary; a recent clinicopathologic series reported TFE3 positivity in 24/26 (92.3%) cases. (zhang2024alveolarsoftpart pages 2-4)

4.4 Epigenetic / transcriptional regulation (recent mechanistic advance; 2024)

A 2024 Cancer Research study mapped ASPS transcriptional/chromatin landscapes and provides direct mechanistic statements in the abstract: - Quote: “ASPSCR1::TFE3 directly interacted with key epigenetic regulators at enhancers and promoters to support ASPS-associated transcription.” (sicinska2024aspscr1tfe3drivesalveolar pages 1-3) - Quote: “cell proliferation was driven by high levels of cyclin D1 expression.” (sicinska2024aspscr1tfe3drivesalveolar pages 1-3) - Therapeutic implication: “combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts.” (sicinska2024aspscr1tfe3drivesalveolar pages 1-3)

4.5 Disease–target associations (knowledge graph)

OpenTargets lists ASPS associations for TFE3 and angiogenesis-related targets (e.g., KDR/VEGFR2, FLT4/VEGFR3, PDGFRB), reflecting both biology and clinical development focus. (OpenTargets Search: Alveolar soft part sarcoma)

5. Environmental information

No specific environmental, lifestyle, or infectious causal contributors were identified in the retrieved evidence.

6. Mechanism / pathophysiology

6.1 Causal chain (current understanding)

1) Initiating lesion: somatic der(17)t(X;17) generates ASPSCR1::TFE3. (fujiwara2023advancesintreatment pages 1-2, sicinska2024aspscr1tfe3drivesalveolar pages 1-3) 2) Fusion-driven transcriptional amplification: ASPSCR1::TFE3 broadly binds active chromatin and sustains programs in cell cycle/proliferation, angiogenesis, and mitochondrial biology. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 8-9) 3) Tumor phenotype: highly vascular tumor microenvironment and slow-growing primary lesions, with high metastatic propensity (lung/bone/brain). (fujiwara2022alveolarsoftpart pages 1-2, spinnato2023imagingfeaturesof pages 1-2) 4) Clinical manifestations: painless deep mass; metastatic symptoms depend on organ involved; brain metastasis is an adverse clinical turning point in real-world cohorts. (fernandes2024realworldoutcomes pages 2-6)

6.2 Key molecular programs and targetable dependencies (2024)

Mechanistic evidence supports targetable tumor-intrinsic and tumor-extrinsic vulnerabilities: - Cyclin D1/CDK4 dependency: palbociclib decreased Ki-67 and halted tumor growth in ASPS PDX; CRISPR targeting supports dependency; CDK4/6 + VEGFR inhibition improved xenograft control. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 13-14) - Angiogenesis program: ASPS super-enhancers and expression profiles include angiogenesis genes (e.g., VEGFA), consistent with clinical activity of anti-angiogenic TKIs. (sicinska2024aspscr1tfe3drivesalveolar pages 8-9, fernandes2024realworldoutcomes pages 2-6)

6.3 Suggested ontology terms

GO biological process (examples): - Angiogenesis (GO:0001525) - Regulation of transcription by RNA polymerase II (GO:0006357) - Cell cycle G1/S transition (GO:0044843) - Mitochondrial biogenesis (GO:0007005)

Cell types (CL, examples): - Mesenchymal cell (CL:0000134) - Endothelial cell (CL:0000115) (relevant to the vascular phenotype)

7. Anatomical structures affected

7.1 Primary anatomical sites

Most commonly deep soft tissues of extremities (often thigh), with additional sites including trunk and head/neck; pediatric cohorts show relatively more head/neck presentations. (fujiwara2023advancesintreatment pages 1-2, wang2024ultrasoundcharacteristicsof pages 1-2)

Suggested UBERON (examples): - Limb (UBERON:0002101) - Thigh (UBERON:0000978) - Head and neck region (UBERON:0000033)

7.2 Secondary organs (metastases)

  • Lung (dominant), bone, brain; liver also occurs in some series. (fujiwara2022alveolarsoftpart pages 1-2, zhang2024alveolarsoftpart pages 2-4, fernandes2024realworldoutcomes pages 2-6)

Suggested UBERON (examples): - Lung (UBERON:0002048) - Bone tissue (UBERON:0002481) - Brain (UBERON:0000955)

8. Temporal development

8.1 Onset

Typically adolescent/young adult onset (peak 15–35), but cases can occur across a wide age range. (fujiwara2023advancesintreatment pages 1-2, zhang2024alveolarsoftpart pages 2-4)

8.2 Progression and course

ASPS often shows slow primary growth but frequent metastasis at diagnosis and ongoing metastatic risk even after localized presentation. - Example: in a registry cohort of localized ASPS, 45% developed distant metastases later. (fujiwara2022alveolarsoftpart pages 1-2)

9. Inheritance and population

9.1 Epidemiology

  • Incidence estimate: ~1 per 10 million population per year (review-level estimate). (fujiwara2023advancesintreatment pages 1-2)
  • Proportion of soft-tissue sarcomas: ~0.2–0.9% (review-level). (fujiwara2023advancesintreatment pages 1-2)

Prevalence estimates were not provided in the retrieved evidence.

9.2 Inheritance

ASPS is not described as a Mendelian inherited disorder in the retrieved sources; it is primarily a sporadic cancer driven by a somatic fusion event.

9.3 Demographics

  • Sex: often female predominance reported in reviews, but cohort-to-cohort variation exists. (fujiwara2023advancesintreatment pages 1-2, fernandes2024realworldoutcomes pages 2-6)
  • Age: concentration in younger patients. (fujiwara2023advancesintreatment pages 1-2)

10. Diagnostics

10.1 Pathology and biomarkers

  • TFE3 IHC: 24/26 positive in a 2024 series; sensitivity high but specificity can vary. (zhang2024alveolarsoftpart pages 2-4, cong2025recentprogressin pages 4-5)
  • Molecular confirmation: FISH/RT-PCR/NGS for ASPSCR1::TFE3; Zhang 2024 detected TFE3 rearrangement in 12 tested patients. (zhang2024alveolarsoftpart pages 2-4)
  • PAS-positive crystals: 20/26 PAS-positive in Zhang 2024. (zhang2024alveolarsoftpart pages 4-7)

10.2 Imaging-based diagnosis (2023–2024 evidence)

ASPS is notable for hypervascular imaging patterns that can mimic vascular malformations. - MRI/US hallmarks (Spinnato 2023): Quote from abstract: “Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3).” (spinnato2023imagingfeaturesof pages 1-2) - Pediatric ultrasound (Wang 2024) describes rich vascularity and misclassification as vascular lesions in some cases; tumors were 50% head/neck and 50% trunk/limbs, with 8/20 metastatic at diagnosis. (wang2024ultrasoundcharacteristicsof pages 1-2, wang2024ultrasoundcharacteristicsof pages 3-6)

10.3 Differential diagnosis

A structured differential diagnosis list was not fully extractable from the retrieved evidence set; however, the need for molecular confirmation (fusion testing) in TFE3-positive or equivocal cases is emphasized due to IHC variability. (cong2025recentprogressin pages 4-5)

11. Outcome / prognosis

11.1 Survival statistics (population-level)

A Japanese population-based study (2006–2017; n=120) reported: - “The 5-year disease-specific survival (DSS) was 68% for all patients and 86% and 62% for localized and metastatic disease, respectively.” (fujiwara2022alveolarsoftpart pages 1-2) - Metastasis at presentation was the only adverse prognostic factor (HR 7.65). (fujiwara2022alveolarsoftpart pages 1-2)

11.2 Real-world outcomes (2024)

A tertiary-center real-world cohort (2016–2023; n=34) reported: - Median PFS on first-line TKI monotherapy: 12 months; median OS in metastatic cohort: 36 months; 3-year OS: 52%. (fernandes2024realworldoutcomes pages 2-6) - Brain metastasis conferred markedly poor outcomes (OS 9.4 vs 56 months). (fernandes2024realworldoutcomes pages 2-6)

11.3 Prognostic factors

In a 2024 clinicopathologic series (n=26), prognosis was significantly correlated with sex, tumor size, and metastasis; multivariable Cox regression identified sex and metastasis as independent prognostic factors. (zhang2024alveolarsoftpart pages 4-7, zhang2024alveolarsoftpart pages 2-4)

12. Treatment

12.1 Standard local therapy

Complete surgical resection is described as the standard approach for localized disease, with radiotherapy considered for inadequate margins or unresectable tumors. (fujiwara2023advancesintreatment pages 1-2)

Suggested MAXO terms (examples): - Surgical excision (MAXO:0001025) - Radiotherapy (MAXO:0000647)

12.2 Systemic therapy: recent developments (prioritizing 2023–2024)

Atezolizumab (PD-L1 inhibitor) — pivotal 2023 evidence

A 2023 investigator-initiated multicenter single-group phase 2 study (NEJM; ClinicalTrials.gov NCT03141684) reported: - Quote: “An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses.” (chen2023atezolizumabforadvanced pages 1-3) - Quote: “the median duration of response was 24.7 months (range, 4.1 to 55.8), and the median progression-free survival was 20.8 months.” (chen2023atezolizumabforadvanced pages 1-3) - Safety: no treatment-related grade 4–5 AEs in the abstract; detailed excerpt indicates grade 3 potentially related AEs in 15% and no discontinuations due to AEs. (chen2023atezolizumabforadvanced pages 1-3, chen2023atezolizumabforadvanced pages 7-8)

Real-world implementation: The same NEJM paper notes FDA approval of atezolizumab based on this study, and ongoing trial infrastructure includes atezolizumab alone or with bevacizumab (NCT03141684). (chen2023atezolizumabforadvanced pages 1-3, NCT03141684 chunk 2)

Visual evidence (trial efficacy figures): Waterfall plot and Kaplan–Meier PFS are provided from the NEJM report. (chen2023atezolizumabforadvanced media 37f80583, chen2023atezolizumabforadvanced media 591ab6cf)

Suggested MAXO terms: - Immune checkpoint inhibitor therapy (MAXO:0001481) - PD-L1 inhibitor therapy (MAXO term may vary by release)

Anti-angiogenic TKIs (VEGFR pathway) — real-world and trial infrastructure

A 2024 real-world cohort found most metastatic patients received TKIs first line, with median PFS 12 months and sunitinib ORR 36%. (fernandes2024realworldoutcomes pages 2-6)

A randomized phase 2 crossover trial comparing cediranib vs sunitinib (NCT01391962; enrollment 34) used ORR and 24-week PFS endpoints and required RECIST-defined progression prior to enrollment, reflecting the clinical need to benchmark TKI activity in ASPS. (NCT01391962 chunk 1)

Suggested MAXO terms: - Tyrosine kinase inhibitor therapy (MAXO:0000943) - Antiangiogenic therapy (MAXO:0000938)

Combination and next-step strategies (mechanism-informed)

A 2024 mechanistic study supports combined targeting of cell-intrinsic CDK4 dependence and cell-extrinsic angiogenesis: - Quote (preclinical): “the combination of palbociclib and sunitinib was significantly more effective than either therapy alone…” (sicinska2024aspscr1tfe3drivesalveolar pages 14-16) This motivates clinical exploration of CDK4/6 inhibitors with anti-angiogenic agents (clinical translation remains investigational in ASPS). (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 13-14)

Suggested MAXO: - CDK4/6 inhibitor therapy (MAXO term may vary)

12.3 Active/landmark clinical trials (selected)

  • NCT03141684 (NCI; started 2017): atezolizumab alone or atezolizumab + bevacizumab; ORR by RECIST v1.1 is the primary endpoint; includes biopsy and imaging procedures. (NCT03141684 chunk 2, NCT03141684 chunk 3)
  • NCT02636725 (PI Jonathan Trent; started 2016): axitinib + pembrolizumab phase 2 single-arm; requires measurable disease and RECIST-defined progression; requires serial core biopsies. (NCT02636725 chunk 2)
  • NCT01391962 (NCI; started 2011): randomized phase 2 cediranib vs sunitinib with crossover; primary endpoints include ORR and 24-week PFS. (NCT01391962 chunk 1)

13. Prevention

No primary prevention strategies are established for ASPS in the retrieved evidence. Secondary/tertiary prevention in practice involves early recognition of hypervascular deep soft-tissue masses, referral to sarcoma centers, and appropriate staging (including chest and, in selected contexts, brain imaging given non-trivial CNS involvement in some cohorts). (spinnato2023imagingfeaturesof pages 1-2, fernandes2024realworldoutcomes pages 2-6)

14. Other species / natural disease

No naturally occurring ASPS analogs in non-human species were identified in the retrieved evidence.

15. Model organisms / preclinical models

Mechanistic work uses ASPS cell lines and xenograft/PDX models. - A 2024 Cancer Research study reports palbociclib effects in ASPS PDX and combination efficacy with sunitinib in xenografts, supporting translational modeling for therapy development. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 13-14)

Recent developments (2023–2024) — key takeaways for a knowledge base

1) Checkpoint blockade is now a central systemic option in advanced ASPS: atezolizumab achieved ORR 37% with durable responses and median PFS 20.8 months, with favorable high-grade toxicity profile (no treatment-related grade 4–5 AEs), and served as the basis for regulatory approval. (chen2023atezolizumabforadvanced pages 1-3, chen2023atezolizumabforadvanced pages 7-8) 2) Real-world data confirm continued importance of anti-angiogenic TKIs and highlight CNS metastasis as a major adverse factor, with median OS 36 months in a heavily metastatic cohort and OS ~9.4 months in those with brain metastases. (fernandes2024realworldoutcomes pages 2-6) 3) Mechanistic 2024 data identify a targetable cell-cycle dependency (Cyclin D1/CDK4) and support combination strategies with angiogenesis inhibition, providing a rational next wave of trial design beyond single-agent VEGFR-TKIs and ICIs. (sicinska2024aspscr1tfe3drivesalveolar pages 1-3, sicinska2024aspscr1tfe3drivesalveolar pages 14-16)

Limitations of the retrieved evidence for this template

  • Formal disease identifiers (MONDO/Orphanet/OMIM/ICD/MeSH) were not available in the retrieved full-text snippets; they should be added from dedicated ontology resources.
  • QoL metrics, prevalence estimates, and comprehensive differential diagnosis lists were not captured in the current evidence set.
  • Some citations above are based on tool-provided excerpts; if a downstream curation workflow requires PMIDs for every item, the DOI-anchored references provided here should be mapped to PMIDs via PubMed.

References

  1. (fujiwara2023advancesintreatment pages 1-2): Tomohiro Fujiwara, Toshiyuki Kunisada, Eiji Nakata, Kenji Nishida, Hiroyuki Yanai, Tomoki Nakamura, Kazuhiro Tanaka, and Toshifumi Ozaki. Advances in treatment of alveolar soft part sarcoma: an updated review. Japanese Journal of Clinical Oncology, 53:1009-1018, Aug 2023. URL: https://doi.org/10.1093/jjco/hyad102, doi:10.1093/jjco/hyad102. This article has 26 citations and is from a peer-reviewed journal.

  2. (fernandes2024realworldoutcomes pages 1-2): Sanal Fernandes, Sameer Rastogi, Kanu Priya Bhatia, Sindhura Chitikela, Shamim A Shamim, Shivanand Gammanagatti, and Adarsh Barwad. Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in north india. ecancermedicalscience, Dec 2024. URL: https://doi.org/10.3332/ecancer.2024.1813, doi:10.3332/ecancer.2024.1813. This article has 1 citations and is from a peer-reviewed journal.

  3. (spinnato2023imagingfeaturesof pages 1-2): Paolo Spinnato, Nicolas Papalexis, Marco Colangeli, Marco Miceli, Amandine Crombé, Anna Parmeggiani, Emanuela Palmerini, Alberto Righi, and Giuseppe Bianchi. Imaging features of alveolar soft part sarcoma: single institution experience and literature review. Clinics and Practice, 13:1369-1382, Nov 2023. URL: https://doi.org/10.3390/clinpract13060123, doi:10.3390/clinpract13060123. This article has 16 citations.

  4. (zhang2024alveolarsoftpart pages 1-2): Yi Zhang, Yuchen Huang, Yanzi Qin, Ningning Yang, Panpan Yang, Nan Li, and Zhenzhong Feng. Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis. Diagnostic Pathology, Jan 2024. URL: https://doi.org/10.1186/s13000-024-01450-z, doi:10.1186/s13000-024-01450-z. This article has 10 citations and is from a peer-reviewed journal.

  5. (cong2025recentprogressin pages 1-2): Nan Cong, Qi Shi, Qingyu Xu, and Lin Zhang. Recent progress in the clinicopathological characteristics of alveolar soft part sarcoma. Frontiers in Medicine, Dec 2025. URL: https://doi.org/10.3389/fmed.2025.1702870, doi:10.3389/fmed.2025.1702870. This article has 0 citations.

  6. (wang2024ultrasoundcharacteristicsof pages 1-2): Siwei Wang, Yu Wang, Jiatong Xu, Qinghua Ren, Yanxiu Hu, Liqun Jia, and Xiaoman Wang. Ultrasound characteristics of alveolar soft part sarcoma in pediatric patients: a retrospective analysis. BMC Cancer, Dec 2024. URL: https://doi.org/10.1186/s12885-024-13262-x, doi:10.1186/s12885-024-13262-x. This article has 2 citations and is from a peer-reviewed journal.

  7. (fujiwara2022alveolarsoftpart pages 1-2): Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki, and Akira Kawai. Alveolar soft part sarcoma: progress toward improvement in survival? a population-based study. BMC Cancer, Aug 2022. URL: https://doi.org/10.1186/s12885-022-09968-5, doi:10.1186/s12885-022-09968-5. This article has 33 citations and is from a peer-reviewed journal.

  8. (fernandes2024realworldoutcomes pages 2-6): Sanal Fernandes, Sameer Rastogi, Kanu Priya Bhatia, Sindhura Chitikela, Shamim A Shamim, Shivanand Gammanagatti, and Adarsh Barwad. Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in north india. ecancermedicalscience, Dec 2024. URL: https://doi.org/10.3332/ecancer.2024.1813, doi:10.3332/ecancer.2024.1813. This article has 1 citations and is from a peer-reviewed journal.

  9. (zhang2024alveolarsoftpart pages 4-7): Yi Zhang, Yuchen Huang, Yanzi Qin, Ningning Yang, Panpan Yang, Nan Li, and Zhenzhong Feng. Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis. Diagnostic Pathology, Jan 2024. URL: https://doi.org/10.1186/s13000-024-01450-z, doi:10.1186/s13000-024-01450-z. This article has 10 citations and is from a peer-reviewed journal.

  10. (zhang2024alveolarsoftpart pages 2-4): Yi Zhang, Yuchen Huang, Yanzi Qin, Ningning Yang, Panpan Yang, Nan Li, and Zhenzhong Feng. Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis. Diagnostic Pathology, Jan 2024. URL: https://doi.org/10.1186/s13000-024-01450-z, doi:10.1186/s13000-024-01450-z. This article has 10 citations and is from a peer-reviewed journal.

  11. (cong2025recentprogressin pages 4-5): Nan Cong, Qi Shi, Qingyu Xu, and Lin Zhang. Recent progress in the clinicopathological characteristics of alveolar soft part sarcoma. Frontiers in Medicine, Dec 2025. URL: https://doi.org/10.3389/fmed.2025.1702870, doi:10.3389/fmed.2025.1702870. This article has 0 citations.

  12. (sicinska2024aspscr1tfe3drivesalveolar pages 1-3): Ewa Sicinska, Vijaya S.R. Kola, Joseph A. Kerfoot, Madeleine L. Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J. Church, Esther Landesman-Bollag, Yosef Landesman, and Matthew L. Hemming. Aspscr1::tfe3 drives alveolar soft part sarcoma by inducing targetable transcriptional programs. Cancer Research, 84:2247-2264, Apr 2024. URL: https://doi.org/10.1158/0008-5472.can-23-2115, doi:10.1158/0008-5472.can-23-2115. This article has 11 citations and is from a highest quality peer-reviewed journal.

  13. (cong2025recentprogressin pages 3-4): Nan Cong, Qi Shi, Qingyu Xu, and Lin Zhang. Recent progress in the clinicopathological characteristics of alveolar soft part sarcoma. Frontiers in Medicine, Dec 2025. URL: https://doi.org/10.3389/fmed.2025.1702870, doi:10.3389/fmed.2025.1702870. This article has 0 citations.

  14. (spinnato2023imagingfeaturesof pages 8-10): Paolo Spinnato, Nicolas Papalexis, Marco Colangeli, Marco Miceli, Amandine Crombé, Anna Parmeggiani, Emanuela Palmerini, Alberto Righi, and Giuseppe Bianchi. Imaging features of alveolar soft part sarcoma: single institution experience and literature review. Clinics and Practice, 13:1369-1382, Nov 2023. URL: https://doi.org/10.3390/clinpract13060123, doi:10.3390/clinpract13060123. This article has 16 citations.

  15. (spinnato2023imagingfeaturesof pages 2-4): Paolo Spinnato, Nicolas Papalexis, Marco Colangeli, Marco Miceli, Amandine Crombé, Anna Parmeggiani, Emanuela Palmerini, Alberto Righi, and Giuseppe Bianchi. Imaging features of alveolar soft part sarcoma: single institution experience and literature review. Clinics and Practice, 13:1369-1382, Nov 2023. URL: https://doi.org/10.3390/clinpract13060123, doi:10.3390/clinpract13060123. This article has 16 citations.

  16. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16): Ewa Sicinska, Vijaya S.R. Kola, Joseph A. Kerfoot, Madeleine L. Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J. Church, Esther Landesman-Bollag, Yosef Landesman, and Matthew L. Hemming. Aspscr1::tfe3 drives alveolar soft part sarcoma by inducing targetable transcriptional programs. Cancer Research, 84:2247-2264, Apr 2024. URL: https://doi.org/10.1158/0008-5472.can-23-2115, doi:10.1158/0008-5472.can-23-2115. This article has 11 citations and is from a highest quality peer-reviewed journal.

  17. (sicinska2024aspscr1tfe3drivesalveolar pages 8-9): Ewa Sicinska, Vijaya S.R. Kola, Joseph A. Kerfoot, Madeleine L. Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J. Church, Esther Landesman-Bollag, Yosef Landesman, and Matthew L. Hemming. Aspscr1::tfe3 drives alveolar soft part sarcoma by inducing targetable transcriptional programs. Cancer Research, 84:2247-2264, Apr 2024. URL: https://doi.org/10.1158/0008-5472.can-23-2115, doi:10.1158/0008-5472.can-23-2115. This article has 11 citations and is from a highest quality peer-reviewed journal.

  18. (sicinska2024aspscr1tfe3drivesalveolar pages 13-14): Ewa Sicinska, Vijaya S.R. Kola, Joseph A. Kerfoot, Madeleine L. Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J. Church, Esther Landesman-Bollag, Yosef Landesman, and Matthew L. Hemming. Aspscr1::tfe3 drives alveolar soft part sarcoma by inducing targetable transcriptional programs. Cancer Research, 84:2247-2264, Apr 2024. URL: https://doi.org/10.1158/0008-5472.can-23-2115, doi:10.1158/0008-5472.can-23-2115. This article has 11 citations and is from a highest quality peer-reviewed journal.

  19. (chen2023atezolizumabforadvanced pages 1-3): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.

  20. (chen2023atezolizumabforadvanced pages 5-7): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.

  21. (chen2023atezolizumabforadvanced pages 7-8): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.

  22. (NCT03141684 chunk 2): Testing Atezolizumab Alone or Atezolizumab Plus Bevacizumab in People With Advanced Alveolar Soft Part Sarcoma. National Cancer Institute (NCI). 2017. ClinicalTrials.gov Identifier: NCT03141684

  23. (NCT03141684 chunk 3): Testing Atezolizumab Alone or Atezolizumab Plus Bevacizumab in People With Advanced Alveolar Soft Part Sarcoma. National Cancer Institute (NCI). 2017. ClinicalTrials.gov Identifier: NCT03141684

  24. (fernandes2024realworldoutcomes pages 6-8): Sanal Fernandes, Sameer Rastogi, Kanu Priya Bhatia, Sindhura Chitikela, Shamim A Shamim, Shivanand Gammanagatti, and Adarsh Barwad. Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in north india. ecancermedicalscience, Dec 2024. URL: https://doi.org/10.3332/ecancer.2024.1813, doi:10.3332/ecancer.2024.1813. This article has 1 citations and is from a peer-reviewed journal.

  25. (NCT02636725 chunk 2): Jonathan Trent, MD, PhD. Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas. Jonathan Trent, MD, PhD. 2016. ClinicalTrials.gov Identifier: NCT02636725

  26. (NCT01391962 chunk 1): Alice Chen, M.D.. Sunitinib or Cediranib for Alveolar Soft Part Sarcoma. National Cancer Institute (NCI). 2011. ClinicalTrials.gov Identifier: NCT01391962

  27. (OpenTargets Search: Alveolar soft part sarcoma): Open Targets Query (Alveolar soft part sarcoma, 42 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  28. (wang2024ultrasoundcharacteristicsof pages 3-6): Siwei Wang, Yu Wang, Jiatong Xu, Qinghua Ren, Yanxiu Hu, Liqun Jia, and Xiaoman Wang. Ultrasound characteristics of alveolar soft part sarcoma in pediatric patients: a retrospective analysis. BMC Cancer, Dec 2024. URL: https://doi.org/10.1186/s12885-024-13262-x, doi:10.1186/s12885-024-13262-x. This article has 2 citations and is from a peer-reviewed journal.

  29. (chen2023atezolizumabforadvanced media 37f80583): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.

  30. (chen2023atezolizumabforadvanced media 591ab6cf): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.