Malignant Mesothelioma

MONDO:0006292 Pathograph 6 mesothelial neoplasm

Malignant mesothelioma is an aggressive cancer arising from mesothelial cells lining the pleural, peritoneal, or pericardial cavities. It is strongly associated with asbestos exposure, with a long latency period of 20-50 years between exposure and disease onset. The disease is characterized by diffuse growth along serosal surfaces, making complete surgical resection difficult. Germline BAP1 mutations define a hereditary cancer syndrome with increased susceptibility to mesothelioma, uveal melanoma, and other malignancies.

Ask OpenScientist

Ask a research question about Malignant Mesothelioma. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).

Submitting...

Do not include personal health information in your question. Questions and results are cached in your browser's local storage.

0
Mappings
0
Definitions
0
Inheritance
4
Pathophysiology
1
Histopathology
5
Phenotypes
6
Pathograph
3
Genes
4
Treatments
3
Subtypes
0
Differentials
0
Datasets
0
Trials
0
Models
9
References
1
Deep Research
🏷

Classifications

Harrison's Chapter
cancer solid tumor
ICD-O Morphology
Carcinoma
◆

Subtypes

3
Epithelioid Mesothelioma
The most common subtype (50-70%), characterized by polygonal cells with abundant cytoplasm arranged in tubulo-papillary, trabecular, or solid patterns. Has the best prognosis among mesothelioma subtypes.
Sarcomatoid Mesothelioma
Accounts for 10-20% of cases. Composed of spindle cells arranged in fascicles resembling fibrosarcoma. Has the worst prognosis with median survival less than one year.
Biphasic Mesothelioma
Contains both epithelioid and sarcomatoid components, each comprising at least 10% of the tumor. Prognosis intermediate between the pure subtypes.
⚙

Pathophysiology

4
Asbestos-Induced Mesothelial Injury
Asbestos fibers penetrate the mesothelium and induce a cycle of cell death and regeneration. The fibers generate reactive oxygen species (ROS) and reactive nitrogen species that damage DNA, proteins, and lipids. Chronic inflammation driven by frustrated phagocytosis of long fibers promotes ongoing tissue damage and malignant transformation.
mesothelial cell link
inflammatory response link ↑ INCREASED response to oxidative stress link ↑ INCREASED
pleura link
BAP1 Tumor Suppressor Inactivation
BAP1 (BRCA1-associated protein 1) is a nuclear deubiquitinase that regulates chromatin remodeling, DNA damage response, and cell cycle progression. BAP1 is one of the most frequently inactivated tumor suppressors in mesothelioma, affected through germline or somatic loss-of-function alterations that predispose to malignant transformation. BAP1 loss impairs chromatin regulation and global gene expression control.
BAP1 link
DNA damage response link ↓ DECREASED
deubiquitinase activity link ↓ DECREASED
Show evidence (2 references)
PMID:23677068 SUPPORT Human Clinical
"The cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF), neurofibromatosis type 2 (NF2) and BRCA1-associated protein-1 (BAP1) genes are the most frequently mutated tumor suppressor genes detected in MM cells"
Sekido's molecular pathogenesis review of malignant mesothelioma identifies BAP1 as one of the most frequently mutated tumor suppressor genes in MM, supporting the claim that BAP1 inactivation is a recurrent driver event.
PMID:23677068 SUPPORT Human Clinical
"BAP1 is involved in histone modification and its inactivation induces the disturbance of global gene expression profiling"
Same review establishes the mechanistic role of BAP1 in chromatin regulation/histone modification, supporting the description of BAP1 as a chromatin-remodeling tumor suppressor whose loss disrupts gene expression.
NF2/Merlin Inactivation
The NF2 gene encoding merlin is frequently inactivated in mesothelioma. Merlin loss activates YAP/TAZ signaling through the Hippo pathway, promoting cell proliferation and inhibiting contact-dependent growth arrest.
NF2 link
Hippo signaling link ↓ DECREASED
Show evidence (2 references)
PMID:23677068 SUPPORT Human Clinical
"The cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF), neurofibromatosis type 2 (NF2) and BRCA1-associated protein-1 (BAP1) genes are the most frequently mutated tumor suppressor genes detected in MM cells"
Sekido's molecular pathogenesis review of malignant mesothelioma identifies NF2 as one of the most frequently mutated tumor suppressor genes in MM, supporting the claim that NF2 inactivation is a recurrent driver event.
PMID:23677068 SUPPORT Human Clinical
"Merlin, which is encoded by NF2, regulates multiple cell signaling cascades including the Hippo and mammalian target of rapamycin pathways, which regulate cell proliferation and growth"
Same review establishes the mechanistic link between NF2/merlin loss and dysregulated Hippo (and mTOR) signaling that drives mesothelioma cell proliferation, supporting the YAP/TAZ activation downstream edge.
CDKN2A/p16 Loss
Homozygous deletion of CDKN2A, encoding p16INK4a and p14ARF, is one of the most frequent genetic alterations in mesothelioma. Loss of p16 removes CDK4/6 inhibition, promoting cell cycle progression, while p14ARF loss compromises p53 stabilization.
CDKN2A link
negative regulation of G1/S transition link ↓ DECREASED
Show evidence (1 reference)
PMID:23677068 SUPPORT Human Clinical
"The cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF), neurofibromatosis type 2 (NF2) and BRCA1-associated protein-1 (BAP1) genes are the most frequently mutated tumor suppressor genes detected in MM cells"
Sekido's molecular pathogenesis review identifies CDKN2A/ARF as one of the most frequently mutated tumor suppressor genes in mesothelioma, supporting the claim that CDKN2A inactivation is a recurrent driver event.
✶

Histopathology

1
Mesothelial Neoplasm VERY_FREQUENT
Malignant mesothelioma is a neoplasm arising from mesothelial cells lining serosal cavities.
Show evidence (1 reference)
PMID:21412769 SUPPORT
"Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining"
Abstract defines malignant mesothelioma as arising from mesothelial cells.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Malignant Mesothelioma 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
Metabolism 1
Pleural Effusion VERY_FREQUENT Pleural effusion (HP:0002202)
Respiratory 1
Dyspnea VERY_FREQUENT Dyspnea (HP:0002094)
Constitutional 2
Chest Pain FREQUENT Chest pain (HP:0100749)
Fatigue FREQUENT Fatigue (HP:0012378)
Growth 1
Weight Loss FREQUENT Weight loss (HP:0001824)
🧬

Genetic Associations

3
BAP1 (Germline and Somatic Mutations)
Autosomal Dominant
NF2 (Somatic Mutations)
CDKN2A (Homozygous Deletion)
💊

Treatments

4
Platinum-Based Chemotherapy
Action: chemotherapy MAXO:0000647
Agent: cisplatin ↗ pemetrexed ↗
First-line treatment combines cisplatin or carboplatin with pemetrexed. This regimen improves median survival from approximately 9 to 12-14 months compared to platinum alone.
Immune Checkpoint Inhibition
Action: immunotherapy Ontology label: Immunotherapy NCIT:C15262
Nivolumab plus ipilimumab is approved for unresectable pleural mesothelioma based on the CheckMate 743 trial, which showed improved overall survival compared to chemotherapy. Response rates are highest in non-epithelioid subtypes.
Show evidence (1 reference)
DOI:10.3390/cancers15245787 SUPPORT Human Clinical
"Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA."
This review summarizes CheckMate-743 survival benefit and regulatory approval for nivolumab plus ipilimumab in first-line malignant pleural mesothelioma.
Surgical Resection
Action: surgical procedure MAXO:0000004
Extended pleurectomy/decortication (EPD) or extrapleural pneumonectomy (EPP) may be considered in select patients with early-stage epithelioid disease. Complete cytoreduction is rarely achievable due to diffuse growth pattern.
Radiation Therapy
Action: radiation therapy MAXO:0000014
Used for palliation of pain and prevention of tumor seeding at intervention sites. Intensity-modulated radiation therapy (IMRT) may be used as adjuvant therapy after surgery in multimodality treatment approaches.
🌍

Environmental Factors

1
Asbestos Exposure
exposure to asbestos link
Asbestos fibers, when inhaled or ingested, become lodged in mesothelial tissues where they cause chronic inflammation, oxidative stress, and DNA damage. The fibers persist indefinitely in tissue and are directly genotoxic, causing chromosomal abnormalities and mesothelial cell transformation. Occupational exposure accounts for approximately 80% of cases.
Show evidence (1 reference)
PMID:23743993 SUPPORT
"Malignant pleural mesothelioma (MPM) is an aggressive, malignant tumor of the pleural surface and is strongly associated with asbestos exposure."
Supports the strong association between mesothelioma and asbestos exposure.
🔬

Biochemical Markers

2
Mesothelin
BAP1 Immunohistochemistry
{ }

Source YAML

click to show 
name: Malignant Mesothelioma
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-05-09T19:42:12Z'
description: >-
  Malignant mesothelioma is an aggressive cancer arising from mesothelial cells
  lining the pleural, peritoneal, or pericardial cavities. It is strongly associated
  with asbestos exposure, with a long latency period of 20-50 years between exposure
  and disease onset. The disease is characterized by diffuse growth along serosal
  surfaces, making complete surgical resection difficult. Germline BAP1 mutations
  define a hereditary cancer syndrome with increased susceptibility to mesothelioma,
  uveal melanoma, and other malignancies.
categories:
- Thoracic Malignancy
- Environmental Cancer
- Occupational Disease
parents:
- mesothelial neoplasm
has_subtypes:
- name: Epithelioid Mesothelioma
  description: >-
    The most common subtype (50-70%), characterized by polygonal cells with
    abundant cytoplasm arranged in tubulo-papillary, trabecular, or solid
    patterns. Has the best prognosis among mesothelioma subtypes.
- name: Sarcomatoid Mesothelioma
  description: >-
    Accounts for 10-20% of cases. Composed of spindle cells arranged in
    fascicles resembling fibrosarcoma. Has the worst prognosis with median
    survival less than one year.
- name: Biphasic Mesothelioma
  description: >-
    Contains both epithelioid and sarcomatoid components, each comprising
    at least 10% of the tumor. Prognosis intermediate between the pure subtypes.
environmental:
- name: Asbestos Exposure
  description: >-
    Asbestos fibers, when inhaled or ingested, become lodged in mesothelial
    tissues where they cause chronic inflammation, oxidative stress, and DNA
    damage. The fibers persist indefinitely in tissue and are directly genotoxic,
    causing chromosomal abnormalities and mesothelial cell transformation.
    Occupational exposure accounts for approximately 80% of cases.
  evidence:
  - reference: PMID:23743993
    reference_title: "[Regional treatment of malignant pleural mesothelioma: results from the tumor centre Regensburg]."
    supports: SUPPORT
    snippet: "Malignant pleural mesothelioma (MPM) is an aggressive, malignant tumor of the pleural surface and is strongly associated with asbestos exposure."
    explanation: "Supports the strong association between mesothelioma and asbestos exposure."
  exposure_term:
    preferred_term: exposure to asbestos
    term:
      id: ECTO:9000033
      label: exposure to asbestos
pathophysiology:
- name: Asbestos-Induced Mesothelial Injury
  description: >-
    Asbestos fibers penetrate the mesothelium and induce a cycle of cell death
    and regeneration. The fibers generate reactive oxygen species (ROS) and
    reactive nitrogen species that damage DNA, proteins, and lipids. Chronic
    inflammation driven by frustrated phagocytosis of long fibers promotes
    ongoing tissue damage and malignant transformation.
  cell_types:
  - preferred_term: mesothelial cell
    term:
      id: CL:0000077
      label: mesothelial cell
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: response to oxidative stress
    modifier: INCREASED
    term:
      id: GO:0006979
      label: response to oxidative stress
  locations:
  - preferred_term: pleura
    term:
      id: UBERON:0000977
      label: pleura
- name: BAP1 Tumor Suppressor Inactivation
  description: >-
    BAP1 (BRCA1-associated protein 1) is a nuclear deubiquitinase that regulates
    chromatin remodeling, DNA damage response, and cell cycle progression. BAP1
    is one of the most frequently inactivated tumor suppressors in mesothelioma,
    affected through germline or somatic loss-of-function alterations that
    predispose to malignant transformation. BAP1 loss impairs chromatin
    regulation and global gene expression control.
  evidence:
  - reference: PMID:23677068
    reference_title: "Molecular pathogenesis of malignant mesothelioma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF), neurofibromatosis type 2 (NF2) and BRCA1-associated protein-1 (BAP1) genes are the most frequently mutated tumor suppressor genes detected in MM cells"
    explanation: >-
      Sekido's molecular pathogenesis review of malignant mesothelioma identifies
      BAP1 as one of the most frequently mutated tumor suppressor genes in MM,
      supporting the claim that BAP1 inactivation is a recurrent driver event.
  - reference: PMID:23677068
    reference_title: "Molecular pathogenesis of malignant mesothelioma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BAP1 is involved in histone modification and its inactivation induces the disturbance of global gene expression profiling"
    explanation: >-
      Same review establishes the mechanistic role of BAP1 in chromatin
      regulation/histone modification, supporting the description of BAP1 as a
      chromatin-remodeling tumor suppressor whose loss disrupts gene expression.
  genes:
  - preferred_term: BAP1
    term:
      id: hgnc:950
      label: BAP1
  molecular_functions:
  - preferred_term: deubiquitinase activity
    modifier: DECREASED
    term:
      id: GO:0101005
      label: deubiquitinase activity
  biological_processes:
  - preferred_term: DNA damage response
    modifier: DECREASED
    term:
      id: GO:0006974
      label: DNA damage response
- name: NF2/Merlin Inactivation
  description: >-
    The NF2 gene encoding merlin is frequently inactivated in mesothelioma.
    Merlin loss activates YAP/TAZ signaling through the Hippo pathway,
    promoting cell proliferation and inhibiting contact-dependent growth
    arrest.
  evidence:
  - reference: PMID:23677068
    reference_title: "Molecular pathogenesis of malignant mesothelioma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF), neurofibromatosis type 2 (NF2) and BRCA1-associated protein-1 (BAP1) genes are the most frequently mutated tumor suppressor genes detected in MM cells"
    explanation: >-
      Sekido's molecular pathogenesis review of malignant mesothelioma identifies
      NF2 as one of the most frequently mutated tumor suppressor genes in MM,
      supporting the claim that NF2 inactivation is a recurrent driver event.
  - reference: PMID:23677068
    reference_title: "Molecular pathogenesis of malignant mesothelioma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Merlin, which is encoded by NF2, regulates multiple cell signaling cascades including the Hippo and mammalian target of rapamycin pathways, which regulate cell proliferation and growth"
    explanation: >-
      Same review establishes the mechanistic link between NF2/merlin loss and
      dysregulated Hippo (and mTOR) signaling that drives mesothelioma cell
      proliferation, supporting the YAP/TAZ activation downstream edge.
  genes:
  - preferred_term: NF2
    term:
      id: hgnc:7773
      label: NF2
  biological_processes:
  - preferred_term: Hippo signaling
    modifier: DECREASED
    term:
      id: GO:0035329
      label: hippo signaling
- name: CDKN2A/p16 Loss
  description: >-
    Homozygous deletion of CDKN2A, encoding p16INK4a and p14ARF, is one of the
    most frequent genetic alterations in mesothelioma. Loss of p16 removes
    CDK4/6 inhibition, promoting cell cycle progression, while p14ARF loss
    compromises p53 stabilization.
  evidence:
  - reference: PMID:23677068
    reference_title: "Molecular pathogenesis of malignant mesothelioma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The cyclin-dependent kinase inhibitor 2A/alternative reading frame (CDKN2A/ARF), neurofibromatosis type 2 (NF2) and BRCA1-associated protein-1 (BAP1) genes are the most frequently mutated tumor suppressor genes detected in MM cells"
    explanation: >-
      Sekido's molecular pathogenesis review identifies CDKN2A/ARF as one of
      the most frequently mutated tumor suppressor genes in mesothelioma,
      supporting the claim that CDKN2A inactivation is a recurrent driver
      event.
  genes:
  - preferred_term: CDKN2A
    term:
      id: hgnc:1787
      label: CDKN2A
  biological_processes:
  - preferred_term: negative regulation of G1/S transition
    modifier: DECREASED
    term:
      id: GO:2000134
      label: negative regulation of G1/S transition of mitotic cell cycle
histopathology:
- name: Mesothelial Neoplasm
  finding_term:
    preferred_term: Mesothelial Neoplasm
    term:
      id: NCIT:C3786
      label: Mesothelial Neoplasm
  frequency: VERY_FREQUENT
  description: Malignant mesothelioma is a neoplasm arising from mesothelial cells lining serosal cavities.
  evidence:
  - reference: PMID:21412769
    reference_title: "Malignant mesothelioma: facts, myths, and hypotheses."
    supports: SUPPORT
    snippet: "Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining"
    explanation: Abstract defines malignant mesothelioma as arising from mesothelial cells.

phenotypes:
- category: Pulmonary
  name: Dyspnea
  frequency: VERY_FREQUENT
  description: >-
    Progressive shortness of breath is the most common presenting symptom,
    typically caused by pleural effusion and tumor encasement of the lung.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
- category: Pulmonary
  name: Pleural Effusion
  frequency: VERY_FREQUENT
  description: >-
    Accumulation of fluid in the pleural space occurs in 80-95% of patients
    at presentation. The effusion is typically exudative and may be bloody.
  phenotype_term:
    preferred_term: Pleural effusion
    term:
      id: HP:0002202
      label: Pleural effusion
- category: Thoracic
  name: Chest Pain
  frequency: FREQUENT
  description: >-
    Dull, aching chest wall pain results from tumor invasion of the parietal
    pleura and chest wall. Pain may be localized or diffuse.
  phenotype_term:
    preferred_term: Chest pain
    term:
      id: HP:0100749
      label: Chest pain
- category: Constitutional
  name: Weight Loss
  frequency: FREQUENT
  description: >-
    Unintentional weight loss occurs as disease progresses and is associated
    with poor prognosis.
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
- category: Constitutional
  name: Fatigue
  frequency: FREQUENT
  description: >-
    Cancer-related fatigue is common and may be exacerbated by anemia,
    dyspnea, and cachexia.
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
biochemical:
- name: Mesothelin
  biomarker_term:
    preferred_term: Mesothelin
    term:
      id: NCIT:C20887
      label: Mesothelin
  notes: >-
    Serum mesothelin and megakaryocyte potentiating factor (MPF) are elevated
    in mesothelioma and can be used for diagnosis and monitoring. Sensitivity
    is approximately 60% for epithelioid subtype but lower for sarcomatoid.
- name: BAP1 Immunohistochemistry
  notes: >-
    Loss of nuclear BAP1 staining by immunohistochemistry indicates BAP1
    inactivation and supports the diagnosis of mesothelioma over reactive
    mesothelial proliferation.
genetic:
- name: BAP1
  association: Germline and Somatic Mutations
  inheritance:
  - name: Autosomal Dominant
  notes: >-
    Germline BAP1 mutations define the BAP1 tumor predisposition syndrome with
    increased risk of mesothelioma (pleural and peritoneal), uveal melanoma,
    cutaneous melanoma, and renal cell carcinoma. Somatic BAP1 loss occurs in
    60-70% of sporadic mesotheliomas.
- name: NF2
  association: Somatic Mutations
  notes: >-
    NF2 inactivation through mutation, deletion, or methylation occurs in
    approximately 50% of mesotheliomas. Encodes merlin, a tumor suppressor
    regulating the Hippo pathway.
- name: CDKN2A
  association: Homozygous Deletion
  notes: >-
    CDKN2A homozygous deletion is the most common genetic alteration in
    mesothelioma (approximately 70%). FISH detection of CDKN2A deletion
    helps distinguish malignant from reactive mesothelial proliferation.
treatments:
- name: Platinum-Based Chemotherapy
  description: >-
    First-line treatment combines cisplatin or carboplatin with pemetrexed.
    This regimen improves median survival from approximately 9 to 12-14 months
    compared to platinum alone.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: MAXO:0000647
      label: chemotherapy
    therapeutic_agent:
    - preferred_term: cisplatin
      term:
        id: CHEBI:27899
        label: cisplatin
    - preferred_term: pemetrexed
      term:
        id: CHEBI:63616
        label: pemetrexed
- name: Immune Checkpoint Inhibition
  description: >-
    Nivolumab plus ipilimumab is approved for unresectable pleural mesothelioma
    based on the CheckMate 743 trial, which showed improved overall survival
    compared to chemotherapy. Response rates are highest in non-epithelioid
    subtypes.
  treatment_term:
    preferred_term: immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
  evidence:
  - reference: DOI:10.3390/cancers15245787
    reference_title: "Malignant Pleural Mesothelioma: An Update"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Recently, in first-line treatment, immunotherapy combining nivolumab with
      ipilimumab has been shown to be superior to chemotherapy in the
      CheckMate-743 study in terms of overall survival (18.1 months), leading to
      its approval by the FDA and EMA.
    explanation: >-
      This review summarizes CheckMate-743 survival benefit and regulatory
      approval for nivolumab plus ipilimumab in first-line malignant pleural
      mesothelioma.
- name: Surgical Resection
  description: >-
    Extended pleurectomy/decortication (EPD) or extrapleural pneumonectomy (EPP)
    may be considered in select patients with early-stage epithelioid disease.
    Complete cytoreduction is rarely achievable due to diffuse growth pattern.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
- name: Radiation Therapy
  description: >-
    Used for palliation of pain and prevention of tumor seeding at intervention
    sites. Intensity-modulated radiation therapy (IMRT) may be used as adjuvant
    therapy after surgery in multimodality treatment approaches.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
disease_term:
  preferred_term: malignant mesothelioma
  term:
    id: MONDO:0006292
    label: malignant mesothelioma

classifications:
  icdo_morphology:
    classification_value: Carcinoma
  harrisons_chapter:
  - classification_value: cancer
  - classification_value: solid tumor
references:
- reference: DOI:10.1200/jco-24-02425
  title: 'Treatment of Pleural Mesothelioma: ASCO Guideline Update'
  found_in:
  - Malignant_Mesothelioma-deep-research-falcon.md
  findings:
  - statement: ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual .
    supporting_text: ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual .
    evidence:
    - reference: DOI:10.1200/jco-24-02425
      reference_title: 'Treatment of Pleural Mesothelioma: ASCO Guideline Update'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual .
      explanation: Deep research cited this publication as relevant literature for Malignant Mesothelioma.
- reference: DOI:10.3390/cancers15245787
  title: Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy
  found_in:
  - Malignant_Mesothelioma-deep-research-falcon.md
  findings:
  - statement: Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months.
    supporting_text: Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months.
    evidence:
    - reference: DOI:10.3390/cancers15245787
      reference_title: Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months.
      explanation: Deep research cited this publication as relevant literature for Malignant Mesothelioma.
- reference: DOI:10.3390/cancers15245808
  title: The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions
  found_in:
  - Malignant_Mesothelioma-deep-research-falcon.md
  findings:
  - statement: The incidence of malignant pleural mesothelioma is expected to increase globally.
    supporting_text: The incidence of malignant pleural mesothelioma is expected to increase globally.
    evidence:
    - reference: DOI:10.3390/cancers15245808
      reference_title: The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The incidence of malignant pleural mesothelioma is expected to increase globally.
      explanation: Deep research cited this publication as relevant literature for Malignant Mesothelioma.
- reference: DOI:10.3390/cancers17193199
  title: 'Perioperative Treatments in Pleural Mesothelioma: State of the Art and Future Directions'
  found_in:
  - Malignant_Mesothelioma-deep-research-falcon.md
  findings:
  - statement: Pleural Mesothelioma (PM) remains a challenging malignancy associated with asbestos exposure and characterized by poor prognosis.
    supporting_text: Pleural Mesothelioma (PM) remains a challenging malignancy associated with asbestos exposure and characterized by poor prognosis.
    evidence:
    - reference: DOI:10.3390/cancers17193199
      reference_title: 'Perioperative Treatments in Pleural Mesothelioma: State of the Art and Future Directions'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Pleural Mesothelioma (PM) remains a challenging malignancy associated with asbestos exposure and characterized by poor prognosis.
      explanation: Deep research cited this publication as relevant literature for Malignant Mesothelioma.
- reference: DOI:10.3390/diagnostics15111323
  title: 'Molecular Insights into Pleural Mesothelioma: Unveiling Pathogenic Mechanisms and Therapeutic Opportunities'
  found_in:
  - Malignant_Mesothelioma-deep-research-falcon.md
  findings:
  - statement: Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies.
    supporting_text: Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies.
    evidence:
    - reference: DOI:10.3390/diagnostics15111323
      reference_title: 'Molecular Insights into Pleural Mesothelioma: Unveiling Pathogenic Mechanisms and Therapeutic Opportunities'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies.
      explanation: Deep research cited this publication as relevant literature for Malignant Mesothelioma.
- reference: DOI:10.3390/ijms251910861
  title: 'Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies'
  found_in:
  - Malignant_Mesothelioma-deep-research-falcon.md
  findings:
  - statement: Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%.
    supporting_text: Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%.
    evidence:
    - reference: DOI:10.3390/ijms251910861
      reference_title: 'Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%.
      explanation: Deep research cited this publication as relevant literature for Malignant Mesothelioma.
- reference: DOI:10.3390/jcm13195837
  title: 'Malignant Pleural Mesothelioma: A Comprehensive Review'
  found_in:
  - Malignant_Mesothelioma-deep-research-falcon.md
  findings:
  - statement: Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body’s external surfaces.
    supporting_text: Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body’s external surfaces.
    evidence:
    - reference: DOI:10.3390/jcm13195837
      reference_title: 'Malignant Pleural Mesothelioma: A Comprehensive Review'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body’s external surfaces.
      explanation: Deep research cited this publication as relevant literature for Malignant Mesothelioma.
- reference: DOI:10.5603/ocp.100725
  title: Diagnosis and treatment of pleural mesothelioma. State of the art 2024
  found_in:
  - Malignant_Mesothelioma-deep-research-falcon.md
  findings:
  - statement: Diagnosis and treatment of pleural mesothelioma. State of the art 2024
    supporting_text: Diagnosis and treatment of pleural mesothelioma. State of the art 2024
- reference: DOI:10.6004/jnccn.2023.0045
  title: 'Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology'
  found_in:
  - Malignant_Mesothelioma-deep-research-falcon.md
  findings:
  - statement: Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites.
    supporting_text: Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites.
    evidence:
    - reference: DOI:10.6004/jnccn.2023.0045
      reference_title: 'Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology'
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites.
      explanation: Deep research cited this publication as relevant literature for Malignant Mesothelioma.
📚

References & Deep Research

References

9
DOI:10.1200/jco-24-02425
Treatment of Pleural Mesothelioma: ASCO Guideline Update
1 finding
ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual .
"ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual ."
Show evidence (1 reference)
DOI:10.1200/jco-24-02425 SUPPORT Other
"ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual ."
Deep research cited this publication as relevant literature for Malignant Mesothelioma.
DOI:10.3390/cancers15245787
Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy
1 finding
Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months.
"Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months."
Show evidence (1 reference)
DOI:10.3390/cancers15245787 SUPPORT Human Clinical
"Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months."
Deep research cited this publication as relevant literature for Malignant Mesothelioma.
DOI:10.3390/cancers15245808
The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions
1 finding
The incidence of malignant pleural mesothelioma is expected to increase globally.
"The incidence of malignant pleural mesothelioma is expected to increase globally."
Show evidence (1 reference)
DOI:10.3390/cancers15245808 SUPPORT Human Clinical
"The incidence of malignant pleural mesothelioma is expected to increase globally."
Deep research cited this publication as relevant literature for Malignant Mesothelioma.
DOI:10.3390/cancers17193199
Perioperative Treatments in Pleural Mesothelioma: State of the Art and Future Directions
1 finding
Pleural Mesothelioma (PM) remains a challenging malignancy associated with asbestos exposure and characterized by poor prognosis.
"Pleural Mesothelioma (PM) remains a challenging malignancy associated with asbestos exposure and characterized by poor prognosis."
Show evidence (1 reference)
DOI:10.3390/cancers17193199 SUPPORT Human Clinical
"Pleural Mesothelioma (PM) remains a challenging malignancy associated with asbestos exposure and characterized by poor prognosis."
Deep research cited this publication as relevant literature for Malignant Mesothelioma.
DOI:10.3390/diagnostics15111323
Molecular Insights into Pleural Mesothelioma: Unveiling Pathogenic Mechanisms and Therapeutic Opportunities
1 finding
Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies.
"Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies."
Show evidence (1 reference)
DOI:10.3390/diagnostics15111323 SUPPORT Human Clinical
"Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies."
Deep research cited this publication as relevant literature for Malignant Mesothelioma.
DOI:10.3390/ijms251910861
Immunotherapy for Treatment of Pleural Mesothelioma: Current and Emerging Therapeutic Strategies
1 finding
Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%.
"Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%."
Show evidence (1 reference)
DOI:10.3390/ijms251910861 SUPPORT Other
"Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%."
Deep research cited this publication as relevant literature for Malignant Mesothelioma.
DOI:10.3390/jcm13195837
Malignant Pleural Mesothelioma: A Comprehensive Review
1 finding
Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body’s external surfaces.
"Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body’s external surfaces."
Show evidence (1 reference)
DOI:10.3390/jcm13195837 SUPPORT Other
"Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body’s external surfaces."
Deep research cited this publication as relevant literature for Malignant Mesothelioma.
DOI:10.5603/ocp.100725
Diagnosis and treatment of pleural mesothelioma. State of the art 2024
1 finding
Diagnosis and treatment of pleural mesothelioma. State of the art 2024
"Diagnosis and treatment of pleural mesothelioma. State of the art 2024"
DOI:10.6004/jnccn.2023.0045
Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology
1 finding
Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites.
"Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites."
Show evidence (1 reference)
DOI:10.6004/jnccn.2023.0045 SUPPORT Other
"Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites."
Deep research cited this publication as relevant literature for Malignant Mesothelioma.

Deep Research

1
Falcon ▸
1. Disease Information
Edison Scientific Literature 29 citations 2026-05-09T11:54:45.275481

1. Disease Information

1.1 Definition and overview

  • Definition: MM is a malignant tumor arising from mesothelial lining cells of serosal membranes (pleura most commonly; also peritoneum and other sites). (zahiu2025molecularinsightsinto pages 1-2, ettinger2023mesotheliomaperitonealversion pages 1-2)
  • Site distribution: Pleura is affected in ~80–85% of cases; peritoneum is less common. (zahiu2025molecularinsightsinto pages 1-2)
  • Terminology evolution: NCCN notes that the term “malignant” is no longer used to classify mesotheliomas because all mesotheliomas are now defined as malignant. (ettinger2023mesotheliomaperitonealversion pages 1-2)

1.2 Key identifiers (ontology/coding)

The retrieved full texts did not contain MONDO/MeSH/ICD/Orphanet codes. These should be populated directly from those terminology resources. - MONDO: not found in retrieved sources (zahiu2025molecularinsightsinto pages 1-2, ettinger2023mesotheliomaperitonealversion pages 1-2) - MeSH: not found in retrieved sources (zahiu2025molecularinsightsinto pages 1-2, ettinger2023mesotheliomaperitonealversion pages 1-2) - ICD-10 / ICD-11: not found in retrieved sources (zahiu2025molecularinsightsinto pages 1-2, ettinger2023mesotheliomaperitonealversion pages 1-2) - Orphanet: not found in retrieved sources (zahiu2025molecularinsightsinto pages 1-2, ettinger2023mesotheliomaperitonealversion pages 1-2)

1.3 Synonyms / alternative names (common in practice)

  • “Malignant pleural mesothelioma (MPM)” (cedres2023currentstateofthearttherapy pages 1-2, jain2024malignantpleuralmesothelioma pages 1-2)
  • “Pleural mesothelioma (PM)” (lewandowska2024diagnosisandtreatment pages 1-2)
  • “Peritoneal mesothelioma (PeM)” (ettinger2023mesotheliomaperitonealversion pages 1-2)

1.4 Evidence provenance (patient-level vs aggregated)

  • The information summarized here is primarily from aggregated disease-level resources: narrative/systematic reviews and clinical practice guidelines, as well as registry-based epidemiology. (cedres2023currentstateofthearttherapy pages 1-2, chiec2024immunotherapyfortreatment pages 1-2, jain2024malignantpleuralmesothelioma pages 1-2, bertin2023thecurrenttreatment pages 1-2, lewandowska2024diagnosisandtreatment pages 1-2, ettinger2023mesotheliomaperitonealversion pages 1-2, OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma)

2. Etiology

2.1 Primary causal factors

Environmental/occupational exposure - Asbestos exposure is repeatedly identified as the dominant causal factor for pleural mesothelioma, with some reviews stating >80% of pleural cases are linked to asbestos. (bertin2023thecurrenttreatment pages 1-2, cedres2023currentstateofthearttherapy pages 1-2) - A dose–response relationship is emphasized in pleural mesothelioma: cumulative exposure, duration, and long latency increase risk. (zahiu2025molecularinsightsinto pages 1-2)

Genetic predisposition - Germline BAP1 pathogenic variants are highlighted as an important inherited risk factor; ASCO notes mesothelioma patients “often have germline mutations, most commonly in…BAP1,” supporting offering germline testing broadly. (kindler2025treatmentofpleural pages 2-3)

2.2 Risk factors (genetic + environmental)

  • Environmental: inhalational asbestos exposure with latency often 15–40 years (reported for pleural mesothelioma). (chiec2024immunotherapyfortreatment pages 1-2)
  • Demographic: male predominance (~70% male in one 2025 review summary; similar directionality in other sources). (zahiu2025molecularinsightsinto pages 1-2)
  • Histology and stage influence prognosis and are part of risk stratification rather than causal risk (epithelioid vs sarcomatoid). (chiec2024immunotherapyfortreatment pages 1-2, lewandowska2024diagnosisandtreatment pages 1-2)

2.3 Protective factors

No protective genetic or environmental factors were explicitly identified in the retrieved sources.

2.4 Gene–environment interaction

A clinically important interaction is suggested by the co-occurrence of strong environmental exposure (asbestos) with genetic susceptibility (BAP1). While detailed gene–environment quantitative interaction models were not present in the retrieved excerpts, the guideline-level emphasis on universal germline testing implies that inherited susceptibility can meaningfully alter risk and counseling, especially in asbestos-exposed populations. (kindler2025treatmentofpleural pages 2-3, lewandowska2024diagnosisandtreatment pages 1-2)

3. Phenotypes

3.1 Key symptoms/signs (with suggested HPO mapping)

Common pleural presentations include dyspnea, pleural effusion, chest pain, cough, and weight loss. Jain et al. (2024) reports pleural effusion in ~90% of patients and lists dyspnea, chest pain, cough, weight loss, and chest wall masses as common presenting features. (jain2024malignantpleuralmesothelioma pages 1-2)

Phenotype (plain language) Suggested HPO term label HPO ID Frequency/notes Typical context (pleural vs peritoneal) Evidence type (human clinical/review)
Shortness of breath / dyspnea Dyspnea Common presenting symptom; reported among common features and in one review as part of symptoms occurring in ~90% with pain Pleural Human clinical/review (jain2024malignantpleuralmesothelioma pages 1-2, tyagi2024germlinebap1mutation pages 14-17)
Pleural effusion Pleural effusion ~90% of patients in one review; right-sided in ~60% in another source Pleural Human clinical/review (jain2024malignantpleuralmesothelioma pages 1-2, tyagi2024germlinebap1mutation pages 14-17)
Chest pain / chest wall pain Chest pain Common; grouped with dyspnea/pain among major presenting symptoms; adverse prognostic factor in one source Pleural Human clinical/review (jain2024malignantpleuralmesothelioma pages 1-2, tyagi2024germlinebap1mutation pages 14-17, tyagi2024germlinebap1mutation pages 11-14)
Cough Cough Common presenting symptom; can be unproductive in pleural mesothelioma Pleural Human clinical/review (jain2024malignantpleuralmesothelioma pages 1-2, tyagi2024germlinebap1mutation pages 11-14, tyagi2024germlinebap1mutation pages 14-17)
Weight loss Weight loss Common presenting feature Pleural Human clinical/review (jain2024malignantpleuralmesothelioma pages 1-2)
Chest wall mass Thoracic mass Reported as a presenting manifestation Pleural Human clinical/review (jain2024malignantpleuralmesothelioma pages 1-2)
Abdominal distension Abdominal distension Reported for peritoneal mesothelioma presentations Peritoneal Human clinical/review (tyagi2024germlinebap1mutation pages 14-17)
Abdominal pain Abdominal pain Reported for peritoneal mesothelioma presentations Peritoneal Human clinical/review (tyagi2024germlinebap1mutation pages 14-17)
Disseminated malignant process at diagnosis Neoplasm of the pleura Often disseminated at diagnosis because of long latency and late presentation Mainly pleural Human clinical/review (lewandowska2024diagnosisandtreatment pages 1-2)
Poor performance status / functional decline Reduced performance status Reported as a negative prognostic feature rather than a diagnostic symptom Pleural/peritoneal Human clinical/review (lewandowska2024diagnosisandtreatment pages 1-2, tyagi2024germlinebap1mutation pages 11-14)
Hyperleukocytosis / elevated white blood cell count Leukocytosis Negative prognostic factor; one source specifies WBC ≥8.3×10^9/L Pleural/peritoneal Human clinical/review (lewandowska2024diagnosisandtreatment pages 1-2, tyagi2024germlinebap1mutation pages 11-14)
Elevated C-reactive protein Increased circulating C-reactive protein concentration Negative prognostic factor in pleural mesothelioma Pleural Human clinical/review (lewandowska2024diagnosisandtreatment pages 1-2)
Thrombocytosis Thrombocytosis Negative prognostic factor; one source specifies platelet count >400,000/µL Pleural/peritoneal Human clinical/review (tyagi2024germlinebap1mutation pages 11-14, tyagi2024germlinebap1mutation pages 14-17)
Elevated lactate dehydrogenase Increased circulating lactate dehydrogenase concentration Negative prognostic factor; one source specifies LDH >500 IU/L Pleural/peritoneal Human clinical/review (tyagi2024germlinebap1mutation pages 11-14, tyagi2024germlinebap1mutation pages 14-17)
Low hemoglobin / anemia Anemia Reported as a poor prognostic feature in one source Pleural/peritoneal Human clinical/review (tyagi2024germlinebap1mutation pages 14-17)

Table: This table summarizes key clinical symptoms, signs, and laboratory abnormalities reported in the retrieved mesothelioma sources, organized by likely HPO mapping and disease context. It is useful for populating phenotype fields in a disease knowledge base while retaining source-linked evidence.

3.2 Onset, severity, progression

  • Latency/onset: symptom onset often occurs decades after exposure; latency estimates include 15–40 years (pleural; Chiec 2024), ~30 years on average (Lewandowska 2024), and 10–50 years (Jain 2024). (chiec2024immunotherapyfortreatment pages 1-2, lewandowska2024diagnosisandtreatment pages 1-2, jain2024malignantpleuralmesothelioma pages 1-2)
  • Progression: typically insidious with frequent late-stage dissemination at diagnosis. (lewandowska2024diagnosisandtreatment pages 1-2)

3.3 Quality of life impact

The ASCO guideline update indicates that quality-of-life domains were key outcomes in trials informing recommendations, and that in MARS2 multiple QOL domains favored chemotherapy alone versus surgery + chemo in a randomized comparison. (kindler2025treatmentofpleural pages 3-5)

4. Genetic / Molecular Information

4.1 Key genes and alterations (current consensus)

Mesothelioma genomic landscapes are dominated by tumor suppressor loss-of-function rather than recurrent activating oncogenes. - Commonly altered genes cited in recent reviews include BAP1, CDKN2A, NF2. (cedres2023currentstateofthearttherapy pages 1-2, jain2024malignantpleuralmesothelioma pages 1-2, bertin2023thecurrenttreatment pages 1-2) - OpenTargets disease–target association evidence also links MM/MPM with WT1, BAP1, CDKN2A, SETD2, TP53, LATS1/2, PDCD1, among others, reflecting both diagnostic markers and therapeutic target biology. (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma)

4.2 Somatic vs germline

  • Germline: BAP1 is emphasized as a recurrent germline predisposition gene; ASCO highlights germline mutation prevalence as clinically relevant and supports offering germline testing broadly. (kindler2025treatmentofpleural pages 2-3)
  • Somatic: BAP1, CDKN2A, NF2 recurrently altered in tumor tissue. (cedres2023currentstateofthearttherapy pages 1-2, jain2024malignantpleuralmesothelioma pages 1-2)

4.3 Diagnostic molecular pathology markers

  • BAP1 IHC: loss of nuclear expression is a key marker; one 2024 review notes BAP1 loss by IHC in ~70% of epithelioid pleural mesotheliomas. (chiec2024immunotherapyfortreatment pages 1-2)
  • CDKN2A (p16) deletion: FISH for p16/CDKN2A deletion is described as a gold-standard ancillary diagnostic approach; MTAP is discussed as a practical surrogate. (zahiu2025molecularinsightsinto pages 1-2, chiec2024immunotherapyfortreatment pages 1-2)
  • MTAP IHC surrogate: MTAP loss described as an “almost ideal surrogate” for p16/CDKN2A deletion testing. (zahiu2025molecularinsightsinto pages 1-2)
Gene/marker Alteration type (somatic/germline; LOF/deletion etc.) Clinical use (diagnosis/prognosis/therapy selection) Assay (IHC/FISH/seq) Notes Key citation (author year, PMID if given in context—otherwise leave blank)
BAP1 Frequent loss/inactivation; tumor suppressor alteration; includes germline pathogenic variants and somatic loss Diagnosis, hereditary risk assessment, prognosis IHC; sequencing Loss of nuclear BAP1 expression is highlighted as a key diagnostic marker; ~70% of epithelioid pleural mesotheliomas show BAP1 loss by IHC; germline BAP1 is associated with younger age and better prognosis in some series; ASCO notes mesothelioma often has germline mutations, most commonly BAP1, supporting routine germline testing discussions (chiec2024immunotherapyfortreatment pages 1-2, lewandowska2024diagnosisandtreatment pages 1-2, kindler2025treatmentofpleural pages 2-3) Chiec 2024; Lewandowska 2024; Kindler 2025
MTAP Loss, often reflecting adjacent CDKN2A deletion biology Diagnosis IHC MTAP loss is described as an almost ideal surrogate for gold-standard p16/CDKN2A FISH deletion testing; especially useful when tissue is limited (zahiu2025molecularinsightsinto pages 1-2, chiec2024immunotherapyfortreatment pages 1-2) Zahiu 2025; Chiec 2024
CDKN2A / p16 Homozygous deletion; recurrent chromosomal loss at 9p21 Diagnosis; adverse biology/prognostic context FISH; MTAP IHC surrogate >90% of sarcomatoid pleural mesotheliomas reportedly have CDKN2A homozygous deletion or MTAP loss; p16/CDKN2A FISH is treated as the gold-standard ancillary diagnostic approach in retrieved sources (chiec2024immunotherapyfortreatment pages 1-2, zahiu2025molecularinsightsinto pages 1-2, tyagi2024germlinebap1mutation pages 14-17) Chiec 2024; Zahiu 2025
NF2 Recurrent tumor suppressor loss/inactivation Molecular characterization; prognostic/biologic relevance Sequencing One of the most frequently altered genes in pleural mesothelioma; part of the recurrent chromosome 22q loss pattern described in reviews (cedres2023currentstateofthearttherapy pages 1-2, jain2024malignantpleuralmesothelioma pages 1-2, tyagi2024germlinebap1mutation pages 14-17, OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Cedres 2023; Jain 2024
TP53 Tumor suppressor alteration (subset) Molecular characterization Sequencing Listed among recurrently altered genes/targets in disease-target evidence; less emphasized diagnostically than BAP1/MTAP/CDKN2A in retrieved context (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Open Targets context
SETD2 Tumor suppressor / epigenetic regulator alteration Molecular characterization Sequencing Included among associated targets in disease-target evidence and recent mesothelioma molecular reviews; supports chromatin dysregulation theme (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Open Targets context
LATS1 / LATS2 Tumor suppressor loss/inactivation Molecular characterization Sequencing Included in disease-target associations and reflects Hippo pathway disruption noted in mesothelioma molecular landscapes (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Open Targets context
WT1 Disease-associated marker/target (not framed here as recurrent genomic driver) Diagnostic immunophenotyping context; disease association IHC (typical clinical use), not specified in retrieved text Open Targets lists WT1 among associated targets for malignant mesothelioma; retrieved context does not provide detailed assay-performance claims for this report (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Open Targets context
PD-L1 Protein expression biomarker Prognosis; possible therapy-response exploration IHC PD-L1 expression occurs in ~20–40% of patients and is associated with poorer prognosis, but predictive value for immunotherapy response remains unconfirmed in retrieved reviews (cedres2023currentstateofthearttherapy pages 1-2) Cedres 2023
Tumor mutational burden (TMB) Generally low genomic mutation burden Therapy-selection research biomarker NGS / sequencing Pleural mesothelioma is described as having low TMB, often <2 nonsynonymous mutations/Mb in most samples, contributing to biomarker challenges for immunotherapy (chiec2024immunotherapyfortreatment pages 1-2, bertin2023thecurrenttreatment pages 1-2) Chiec 2024; Bertin 2023
BAP1 + MTAP panel Combined loss-marker strategy Diagnostic refinement / cost-effectiveness IHC panel Recent review emphasizes combined BAP1 and MTAP IHC as a practical, cost-effective adjunct for difficult mesothelioma diagnosis (zahiu2025molecularinsightsinto pages 17-19) Zahiu 2025
Broad germline cancer predisposition testing Germline pathogenic variants, especially BAP1 Hereditary cancer risk assessment; family counseling; prognosis Germline sequencing / panel testing ASCO update states mesothelioma patients often harbor germline mutations, most commonly BAP1, and notes universal germline testing should be offered; this is a current implementation-oriented recommendation rather than a single-marker assay claim (kindler2025treatmentofpleural pages 2-3) Kindler 2025

Table: This table summarizes the key molecular and diagnostic markers for mesothelioma retrieved from the available context, including their alteration types, clinical uses, and typical assays. It is useful for knowledge-base population because it distinguishes diagnostic markers from broader molecular features and hereditary risk genes.

4.4 Tumor immune microenvironment / biomarkers

  • The pleural mesothelioma microenvironment is described as relatively immunosuppressive, and PD-L1 expression occurs in ~20–40% of patients and is associated with worse prognosis, though predictive value for immunotherapy response remains unconfirmed. (cedres2023currentstateofthearttherapy pages 1-2)

4.5 Epigenetics and chromatin regulation

  • Evidence of epigenetic/chromatin regulator involvement is supported by recurrent alterations in genes such as SETD2 (OpenTargets association) and the emphasis on tumor suppressor/epigenetic regulator alterations in molecular overviews. (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma)

5. Environmental Information

5.1 Environmental/occupational factors

  • Asbestos remains central in contemporary accounts of pleural mesothelioma pathogenesis and continuing incidence. (lewandowska2024diagnosisandtreatment pages 1-2, bertin2023thecurrenttreatment pages 1-2)
  • A regional Italian surveillance study (Emilia-Romagna, 1996–2023; n=3513 cases) found occupational exposure accounted for 82% of cases overall and increased to 88% in the most recent period; most cases were male (72%) and >65 years (79%). (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma)

5.2 Lifestyle factors

No lifestyle protective or causal factors (e.g., smoking, diet) were specifically extracted from the retrieved sources.

5.3 Infectious agents

No infectious etiologies were identified in retrieved sources.

6. Mechanism / Pathophysiology

6.1 Causal chain (high-level)

  • Trigger: Asbestos exposure (inhalational for pleural disease) with prolonged latency. (chiec2024immunotherapyfortreatment pages 1-2, zahiu2025molecularinsightsinto pages 1-2)
  • Intermediate processes: chronic pleural inflammation and tissue injury, with downstream genomic and cellular dysregulation; Jain (2024) describes free radical generation and disruption of cell division among mechanisms in asbestos-related pleural mesothelioma. (jain2024malignantpleuralmesothelioma pages 1-2)
  • Genomic state: predominance of tumor suppressor losses (BAP1, CDKN2A, NF2), low tumor mutational burden; these features contribute to therapeutic resistance and challenges for biomarker development. (chiec2024immunotherapyfortreatment pages 1-2, bertin2023thecurrenttreatment pages 1-2)

6.2 Immune involvement

  • Immunosuppressive tumor microenvironment described in recent treatment-focused reviews (regulatory immune populations; macrophage/MDSC emphasis in Cedres 2023), potentially contributing to variable immunotherapy response. (cedres2023currentstateofthearttherapy pages 1-2)

6.3 Suggested ontology terms (mechanisms)

GO biological process (suggested; IDs not provided in retrieved text): - inflammatory response; response to oxidative stress; apoptotic process; DNA damage response; chromatin organization

CL cell types (suggested; IDs not provided in retrieved text): - mesothelial cell; tumor-associated macrophage; CD8-positive T cell; regulatory T cell

7. Anatomical Structures Affected

7.1 Primary anatomic sites

  • Pleura (dominant site; 80–85%) (zahiu2025molecularinsightsinto pages 1-2)
  • Peritoneum (less common but major clinical subtype) (ettinger2023mesotheliomaperitonealversion pages 1-2)

7.2 Suggested anatomy ontology mapping

UBERON terms are suggested conceptually but IDs were not present in retrieved sources. - pleura; peritoneum

8. Temporal Development

8.1 Onset pattern

  • Typically adult-onset with a long latency from asbestos exposure. (chiec2024immunotherapyfortreatment pages 1-2, lewandowska2024diagnosisandtreatment pages 1-2)

8.2 Progression and staging

  • Many patients present with advanced/disseminated disease at diagnosis, limiting surgical options. (lewandowska2024diagnosisandtreatment pages 1-2)
  • Standard staging uses TNM for pleural disease; Lewandowska (2024) reproduces TNM categories and indicates surgery is considered mainly for stages I–IIIa. (lewandowska2024diagnosisandtreatment pages 1-2)

9. Inheritance and Population

9.1 Epidemiology (recent statistics)

  • US annual cases reported as ~3,500/year in NCCN overview. (ettinger2023mesotheliomaperitonealversion pages 1-2)
  • Another review cites ~2,500–3,200 new U.S. cases annually and ~38,400 worldwide. (zahiu2025molecularinsightsinto pages 1-2)

9.2 Demographics

  • Male predominance (~70% male reported in one review). (zahiu2025molecularinsightsinto pages 1-2)

9.3 Geographic disparities and real-world data (SEER example)

A SEER analysis (2004–2021; 8519 cases) reported a decline in metropolitan incidence (1.4 to 0.8) and later decline in nonmetropolitan incidence (to 0.5 by 2021), with marked survival disparities: by 2020, 1-year cancer-specific survival 50.3% (metropolitan) vs 27.7% (nonmetropolitan) and HR 1.18 for nonmetropolitan hazard of death. (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma)

Metric Value Population/region Year(s) Source Notes
New cases per year ~2,500–3,200 United States Not specified in excerpt Zahiu et al., 2025 (zahiu2025molecularinsightsinto pages 1-2) Review cites annual U.S. case burden for malignant mesothelioma/pleural mesothelioma.
New cases per year ~3,500 United States Not specified in excerpt NCCN Peritoneal Mesothelioma Guidelines, 2023 (ettinger2023mesotheliomaperitonealversion pages 1-2) NCCN overview states mesothelioma is estimated to occur in approximately 3,500 people in the U.S. every year; includes pleural, peritoneal, and other sites.
New cases ~38,400 Worldwide Not specified in excerpt Zahiu et al., 2025 (zahiu2025molecularinsightsinto pages 1-2) Global annual burden cited in review.
Sex distribution ~70% male Mesothelioma overall Not specified in excerpt Zahiu et al., 2025 (zahiu2025molecularinsightsinto pages 1-2) Other sources in context also note male predominance.
Cases by primary site Pleura 80–85% Mesothelioma overall Not specified in excerpt Zahiu et al., 2025 (zahiu2025molecularinsightsinto pages 1-2) Pleura is the dominant site; peritoneum and other serosal sites are less common.
Latency from asbestos exposure to disease 15–40 years Pleural mesothelioma Not specified in excerpt Chiec & Bruno, 2024 (chiec2024immunotherapyfortreatment pages 1-2) Same context describes disease as primarily caused by inhalational asbestos exposure.
Latency from asbestos exposure to symptoms 10–50 years Malignant pleural mesothelioma Not specified in excerpt Jain et al., 2024 (jain2024malignantpleuralmesothelioma pages 1-2) Broad latency range in review; consistent with long natural history.
Average latency ~30 years Pleural mesothelioma Not specified in excerpt Lewandowska & Kowalski, 2024 (lewandowska2024diagnosisandtreatment pages 1-2) Average latency reported in state-of-the-art review.
5-year overall survival ~12% Pleural mesothelioma Not specified in excerpt Chiec & Bruno, 2024 (chiec2024immunotherapyfortreatment pages 1-2); Bertin et al., 2023 (bertin2023thecurrenttreatment pages 1-2) Chiec review abstract cites 5-year OS of 12%; Bertin review states 5-year survival of only 12%.
5-year overall survival ~10% Malignant pleural mesothelioma Not specified in excerpt Jain et al., 2024 (jain2024malignantpleuralmesothelioma pages 1-2) Slightly lower estimate from another review; likely reflects cohort/case-mix differences.
Untreated median survival 4–8 months Malignant pleural mesothelioma Not specified in excerpt Cedres et al., 2023 (cedres2023currentstateofthearttherapy pages 1-2) Review describes untreated patients as having very poor prognosis.
Untreated median survival 7–10 months Pleural mesothelioma / malignant mesothelioma Not specified in excerpt Zahiu et al., 2025 (zahiu2025molecularinsightsinto pages 1-2) Another review provides a somewhat higher untreated median survival estimate.
Overall survival range 9–18 months Malignant pleural mesothelioma Not specified in excerpt Cedres et al., 2023 (cedres2023currentstateofthearttherapy pages 1-2) Review-level estimate across treated populations/settings.
Life expectancy without radical treatment 9 months Pleural mesothelioma Not specified in excerpt Lewandowska & Kowalski, 2024 (lewandowska2024diagnosisandtreatment pages 1-2) Context states life expectancy for patients not treated with radical intent.
Survival by histology after resection ~19 months epithelioid vs ~4 months sarcomatoid Pleural mesothelioma Not specified in excerpt Chiec & Bruno, 2024 (chiec2024immunotherapyfortreatment pages 1-2) Strong prognostic effect of histologic subtype.
Median survival by histology ~17 months epithelioid vs <7 months sarcomatoid Pleural mesothelioma Not specified in excerpt Lewandowska & Kowalski, 2024 (lewandowska2024diagnosisandtreatment pages 1-2) Histology-associated prognosis in review article.
Metropolitan incidence rate 1.4 to 0.8 per 100,000 U.S. metropolitan areas 2004 to 2021 Didier et al., 2025 (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) SEER-based pleural mesothelioma incidence declined over study period.
Nonmetropolitan incidence rate Stable until 2017, then declined to 0.5 per 100,000 U.S. nonmetropolitan areas 2004 to 2021 Didier et al., 2025 (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Indicates later decline outside metropolitan areas.
1-year cancer-specific survival 50.3% U.S. metropolitan areas By 2020 Didier et al., 2025 (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Pleural mesothelioma; better outcomes than nonmetropolitan areas.
1-year cancer-specific survival 27.7% U.S. nonmetropolitan areas By 2020 Didier et al., 2025 (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Marked disparity versus metropolitan populations.
Relative hazard of death HR 1.18 U.S. nonmetropolitan vs metropolitan 2004 to 2021 cohort Didier et al., 2025 (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Multivariable analysis showed higher hazard of death in nonmetropolitan areas.
Regional registry cases 3,513 total cases; 72% male; 79% age >65 years Emilia-Romagna, Italy 1996–2023 Giacomino et al., 2024 (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma) Occupational exposure accounted for 82% overall and increased from 71% to 88% over periods studied.

Table: This table compiles key epidemiology and prognosis statistics for malignant mesothelioma from the retrieved context, including incidence, survival, latency, sex/site distribution, and geographic disparities. It is useful as a concise evidence summary for knowledge base population and comparative review.

9.4 Inheritance

  • Germline susceptibility is clinically relevant, especially BAP1, motivating guideline support for germline testing. (kindler2025treatmentofpleural pages 2-3, lewandowska2024diagnosisandtreatment pages 1-2)

10. Diagnostics

10.1 Imaging and tissue diagnosis (current practice)

  • Jain (2024) describes diagnostic work-up including contrast-enhanced thoracic CT, thoracoscopic pleural biopsy, thoracentesis with cytology, MRI for diaphragmatic invasion assessment, and PET for metastasis evaluation. (jain2024malignantpleuralmesothelioma pages 1-2)
  • Chiec (2024) emphasizes the difficulty of diagnosis from pleural fluid/small biopsies and supports VATS surgical biopsy and invasive staging approaches (e.g., EBUS) when appropriate. (chiec2024immunotherapyfortreatment pages 1-2)

10.2 Biomarkers and molecular pathology

  • BAP1 IHC and MTAP IHC (surrogate for CDKN2A/p16 FISH) are highlighted as high-value diagnostic adjuncts. (zahiu2025molecularinsightsinto pages 1-2, chiec2024immunotherapyfortreatment pages 1-2)

10.3 Germline testing

  • ASCO guideline update explicitly frames germline mutation prevalence (often BAP1) as rationale that universal germline testing should be offered to patients with mesothelioma. (kindler2025treatmentofpleural pages 2-3)

11. Outcome / Prognosis

11.1 Survival (recently reported values)

  • Untreated median survival: 4–8 months (Cedres 2023) and 7–10 months (Zahiu 2025 review excerpt). (cedres2023currentstateofthearttherapy pages 1-2, zahiu2025molecularinsightsinto pages 1-2)
  • Population 5-year OS frequently cited around ~12% (Bertin 2023; Chiec 2024 abstract). (bertin2023thecurrenttreatment pages 1-2, chiec2024immunotherapyfortreatment pages 1-2)
  • Histology strongly influences outcomes (e.g., epithelioid better than sarcomatoid). (chiec2024immunotherapyfortreatment pages 1-2, lewandowska2024diagnosisandtreatment pages 1-2)

11.2 Prognostic factors

Recent review-level prognostic factors include older age, stage, poor performance status, and inflammatory markers (e.g., CRP, leukocytosis). (lewandowska2024diagnosisandtreatment pages 1-2)

12. Treatment

12.1 Standard systemic therapy (real-world implementation)

  • Chemotherapy backbone: platinum + pemetrexed remains a longstanding standard systemic therapy. (cedres2023currentstateofthearttherapy pages 1-2, chiec2024immunotherapyfortreatment pages 1-2, bertin2023thecurrenttreatment pages 1-2)
  • Bevacizumab addition: Cedres (2023) reports adding bevacizumab to platinum–pemetrexed adds ~2 months to median survival. (cedres2023currentstateofthearttherapy pages 1-2)

12.2 Immunotherapy (major recent development; 2023–2024 emphasis)

  • Cedres (2023) reports first-line nivolumab + ipilimumab improved OS versus chemotherapy in CheckMate-743 with median OS 18.1 months, leading to FDA and EMA approval and a new standard-of-care position. (cedres2023currentstateofthearttherapy pages 1-2)

12.3 Surgery and multimodality therapy

  • Lewandowska (2024) describes tri-modal therapy (surgery + chemotherapy + radiotherapy) as a standard for radical management, but notes stage at diagnosis commonly precludes surgery. (lewandowska2024diagnosisandtreatment pages 1-2)
  • ASCO (2025 update) includes randomized evidence (MARS2) showing aggressive surgery (EPD + adjuvant chemo) did not improve outcomes versus chemotherapy alone, with higher early mortality (30-day 4%, 90-day 9%). (kindler2025treatmentofpleural pages 3-5)

12.4 Guideline algorithms (visual evidence)

The ASCO 2025 update provides structured algorithms for surgical selection and first-line systemic therapy selection (immunotherapy vs chemotherapy based on histology). (kindler2025treatmentofpleural media fd734332, kindler2025treatmentofpleural media c1e908f8, kindler2025treatmentofpleural media 9d842ba2, kindler2025treatmentofpleural media 39f509f9, kindler2025treatmentofpleural media 0889009a)

12.5 Clinical trials (selected; NCT IDs)

  • NCT02899299 (CheckMate 743): Phase 3 randomized open-label trial; nivolumab + ipilimumab vs pemetrexed + cisplatin/carboplatin in unresectable pleural malignant mesothelioma; primary endpoint OS; enrollment 605; includes PD-L1 stratified analyses. (NCT02899299 chunk 1)
  • NCT03918252: Neoadjuvant nivolumab ± ipilimumab for 3 cycles followed by surgery and adjuvant nivolumab for 12 months (phase I/II; active not recruiting per excerpt). (cecchi2025perioperativetreatmentsin pages 9-10)
  • Additional identified trials from clinicaltrials.gov search results (metadata only in this run; full protocol/outcomes not extracted here): NCT04334759 (durvalumab + chemotherapy; phase 3), NCT06097728 (MEDI5752 + carboplatin/pemetrexed; phase 3), NCT04287829 (pembrolizumab + lenvatinib; phase 2). (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma)

12.6 Suggested MAXO terms (treatments)

MAXO IDs were not present in retrieved sources; suggested concepts: - immune checkpoint inhibitor therapy; combination immunotherapy; platinum-based chemotherapy; surgical cytoreduction; radiotherapy; genetic counseling / germline testing

Setting (1L unresectable, perioperative, peritoneal etc.) Modality/regimen Key evidence/trial or guideline Reported outcome metrics in context (median OS etc.) Regulatory/real-world implementation notes Suggested MAXO term
1L unresectable pleural mesothelioma Nivolumab + ipilimumab CheckMate-743; summarized in 2023/2024 reviews and ASCO guideline update (cedres2023currentstateofthearttherapy pages 1-2, lewandowska2024diagnosisandtreatment pages 1-2, kindler2025treatmentofpleural media fd734332) Median OS 18.1 months; superior to chemotherapy in CheckMate-743 (cedres2023currentstateofthearttherapy pages 1-2) Described as FDA/EMA approved and a new standard of care; implemented in routine practice/guidelines, including availability in Poland irrespective of histology (cedres2023currentstateofthearttherapy pages 1-2, lewandowska2024diagnosisandtreatment pages 1-2, kindler2025treatmentofpleural media fd734332)
1L unresectable pleural mesothelioma Platinum + pemetrexed Historical standard systemic therapy in reviews/guidelines (cedres2023currentstateofthearttherapy pages 1-2, chiec2024immunotherapyfortreatment pages 1-2, bertin2023thecurrenttreatment pages 1-2, kindler2025treatmentofpleural media fd734332) Extends survival only by months; comparator arm to immunotherapy in modern algorithms (bertin2023thecurrenttreatment pages 1-2, kindler2025treatmentofpleural media fd734332) Remains standard chemotherapy backbone in guidelines and clinical practice (cedres2023currentstateofthearttherapy pages 1-2, kindler2025treatmentofpleural media fd734332)
1L unresectable pleural mesothelioma Platinum + pemetrexed + bevacizumab Review summary of established regimen (cedres2023currentstateofthearttherapy pages 1-2) Addition of bevacizumab adds about 2 months to median survival (cedres2023currentstateofthearttherapy pages 1-2) Used as an intensified chemotherapy-based option where appropriate; discussed as pre-immunotherapy standard intensification (cedres2023currentstateofthearttherapy pages 1-2)
1L pleural mesothelioma, histology-directed decision making Systemic therapy algorithm: immunotherapy versus chemotherapy based on histology ASCO 2025 Figure 5 / Tables 4-5 (kindler2025treatmentofpleural media fd734332) Figure summarizes selection of ipilimumab+nivolumab versus pemetrexed+platinum based on epithelioid vs nonepithelioid histology; no additional numeric outcome quoted in image summary (kindler2025treatmentofpleural media fd734332) ASCO algorithm indicates first-line implementation in routine practice; nivolumab+ipilimumab especially emphasized for nonepithelioid disease (kindler2025treatmentofpleural media fd734332)
Radical/localized pleural mesothelioma Tri-modal therapy (surgery + chemotherapy + radiotherapy) 2024 state-of-the-art review (lewandowska2024diagnosisandtreatment pages 1-2) Presented as standard for radical management; no pooled OS number in retrieved excerpt (lewandowska2024diagnosisandtreatment pages 1-2) Stage at diagnosis usually precludes surgery in many patients (lewandowska2024diagnosisandtreatment pages 1-2)
Resectable stage I-IIIa pleural mesothelioma Surgery: EPP or PD/EPD 2024 review; ASCO surgical algorithm (lewandowska2024diagnosisandtreatment pages 1-2, kindler2025treatmentofpleural media fd734332) No single survival number for surgery alone in these excerpts; surgery is for selected patients with early-stage disease (lewandowska2024diagnosisandtreatment pages 1-2, kindler2025treatmentofpleural media fd734332) EPD/PD currently favored as lung-sparing approaches in guideline algorithms (kindler2025treatmentofpleural media fd734332)
Pleural mesothelioma surgery comparison Extended pleurectomy/decortication (EPD) + adjuvant chemotherapy versus chemotherapy alone MARS2, summarized in ASCO update (kindler2025treatmentofpleural pages 3-5) Median OS 19.3 months with surgery arm versus 24.8 months with chemotherapy alone; HR for death 1.28; 30-day mortality 4%, 90-day mortality 9% (kindler2025treatmentofpleural pages 3-5) Supports caution with aggressive surgery; guideline context favors careful patient selection and lung-sparing approaches (kindler2025treatmentofpleural pages 3-5, kindler2025treatmentofpleural media fd734332)
Advanced/recurrent pleural mesothelioma Immune checkpoint inhibitors (class effect) 2024 immunotherapy review / emerging strategies (chiec2024immunotherapyfortreatment pages 1-2) Review notes recent dual-checkpoint and chemo-immunotherapy trials changed outcomes, but no specific salvage OS quoted in retrieved excerpt (chiec2024immunotherapyfortreatment pages 1-2) Incorporated into modern pleural mesothelioma treatment landscape; biomarker-guided selection remains unresolved (chiec2024immunotherapyfortreatment pages 1-2)
Previously treated pleural mesothelioma No approved systemic option after 1L (as of 2023 review context) 2023 review (cedres2023currentstateofthearttherapy pages 1-2) Explicitly notes no approved systemic options after first-line treatment in that review excerpt (cedres2023currentstateofthearttherapy pages 1-2) Reflects therapeutic gap and rationale for ongoing trials (cedres2023currentstateofthearttherapy pages 1-2)
Peritoneal mesothelioma NCCN-guided workup/diagnosis/treatment pathways NCCN Peritoneal Mesothelioma v2.2023 (ettinger2023mesotheliomaperitonealversion pages 1-2) No regimen-specific OS in retrieved excerpt (ettinger2023mesotheliomaperitonealversion pages 1-2) NCCN notes rarity and encourages clinical trial participation; “malignant” terminology dropped because all mesotheliomas are now defined as malignant (ettinger2023mesotheliomaperitonealversion pages 1-2)

Table: This table summarizes current mesothelioma treatment approaches and outcome data available in the retrieved context, emphasizing first-line systemic therapy, surgery, and guideline implementation. It is useful for quickly comparing standard regimens, landmark evidence, and practice implications.

13. Prevention

  • Primary prevention is centered on eliminating asbestos exposure; ongoing incidence is consistent with long latency and historical exposure. (lewandowska2024diagnosisandtreatment pages 1-2, zahiu2025molecularinsightsinto pages 1-2)
  • No specific screening program guidance for asymptomatic individuals was extracted from the retrieved excerpts.

14. Other Species / Natural Disease

No other-species naturally occurring disease data were present in the retrieved sources.

15. Model Organisms

No model organism systems were detailed in the retrieved excerpts.

Recent developments (2023–2024) and expert analysis (authoritative synthesis)

  1. First-line immunotherapy became practice-defining. A 2023 state-of-the-art review summarizes CheckMate-743, highlighting nivolumab + ipilimumab median OS 18.1 months and regulatory approval, marking a new standard; subsequent 2024 reviews emphasize broad clinical implementation and ongoing biomarker uncertainty. (cedres2023currentstateofthearttherapy pages 1-2, chiec2024immunotherapyfortreatment pages 1-2, lewandowska2024diagnosisandtreatment pages 1-2)
  2. Diagnostic adjuncts are converging on practical IHC strategies. 2024–2025 reviews highlight BAP1 and MTAP IHC, with MTAP as an “almost ideal surrogate” for CDKN2A deletion testing via p16/CDKN2A FISH, potentially improving diagnostic efficiency where tissue is limited. (zahiu2025molecularinsightsinto pages 1-2, chiec2024immunotherapyfortreatment pages 1-2)
  3. Surgery is being re-evaluated with randomized evidence. ASCO’s guideline update incorporates MARS2 results showing no OS advantage for EPD + chemo vs chemo alone and QOL/cost favoring chemo, supporting more conservative, carefully selected multimodality surgery in specialized centers. (kindler2025treatmentofpleural pages 3-5, kindler2025treatmentofpleural media fd734332)
  4. Hereditary genetics is increasingly guideline-relevant. ASCO emphasizes germline mutations (especially BAP1) in mesothelioma, supporting offering germline testing broadly to guide patient/family risk management. (kindler2025treatmentofpleural pages 2-3)

Required direct quotes from abstracts (supporting key statements)

  • Cedres et al. 2023 (Cancers; Dec 2023): “Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months… Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months) …” https://doi.org/10.3390/cancers15245787 (cedres2023currentstateofthearttherapy pages 1-2)
  • NCCN Peritoneal Mesothelioma v2.2023 (Sep 2023): “Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites.” and “The term ‘malignant’ is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.” https://doi.org/10.6004/jnccn.2023.0045 (ettinger2023mesotheliomaperitonealversion pages 1-2)
  • Chiec & Bruno 2024 (IJMS; Oct 2024): “Pleural mesothelioma is a rare malignancy associated with asbestos exposure and very poor prognosis, with a 5-year overall survival of 12%.” https://doi.org/10.3390/ijms251910861 (chiec2024immunotherapyfortreatment pages 1-2)

Notes on evidence limitations and gaps

  • Ontology codes (MONDO, MeSH, ICD-10/ICD-11, Orphanet, OMIM) were not present in the retrieved full-text excerpts; these should be filled by directly querying those coding/ontology resources rather than inferred. (zahiu2025molecularinsightsinto pages 1-2, ettinger2023mesotheliomaperitonealversion pages 1-2)
  • Several clinical trials were identified by NCT number, but detailed protocol fields/outcome fields were only retrieved in this run for NCT02899299 and NCT03918252. (NCT02899299 chunk 1, cecchi2025perioperativetreatmentsin pages 9-10)

References

  1. (zahiu2025molecularinsightsinto pages 1-2): Teodora Zahiu, Carmen Mihaela Mihu, Bianca A. Bosca, Mariana Mărginean, Lavinia Patricia Mocan, Roxana-Adelina Ștefan, Rada Teodora Suflețel, Carina Mihu, and Carmen Stanca Melincovici. Molecular insights into pleural mesothelioma: unveiling pathogenic mechanisms and therapeutic opportunities. Diagnostics, 15:1323, May 2025. URL: https://doi.org/10.3390/diagnostics15111323, doi:10.3390/diagnostics15111323. This article has 4 citations.

  2. (ettinger2023mesotheliomaperitonealversion pages 1-2): David S. Ettinger, Douglas E. Wood, James Stevenson, Dara L. Aisner, Wallace Akerley, Jessica R. Bauman, Ankit Bharat, Debora S. Bruno, Joe Y. Chang, Lucian R. Chirieac, Malcolm DeCamp, Thomas J. Dilling, Jonathan Dowell, Gregory A. Durm, Scott Gettinger, Travis E. Grotz, Matthew A. Gubens, Aparna Hegde, Rudy P. Lackner, Michael Lanuti, Jules Lin, Billy W. Loo, Christine M. Lovly, Fabien Maldonado, Erminia Massarelli, Daniel Morgensztern, Trey C. Mullikin, Thomas Ng, Gregory A. Otterson, Sandip P. Patel, Tejas Patil, Patricio M. Polanco, Gregory J. Riely, Jonathan Riess, Theresa A. Shapiro, Aditi P. Singh, Alda Tam, Tawee Tanvetyanon, Jane Yanagawa, Stephen C. Yang, Edwin Yau, Kristina M. Gregory, and Miranda Hughes. Mesothelioma: peritoneal, version 2.2023, nccn clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network : JNCCN, 21 9:961-979, Sep 2023. URL: https://doi.org/10.6004/jnccn.2023.0045, doi:10.6004/jnccn.2023.0045. This article has 35 citations.

  3. (cedres2023currentstateofthearttherapy pages 1-2): Susana Cedres, Augusto Valdivia, Patricia Iranzo, Ana Callejo, Nuria Pardo, Alejandro Navarro, Alex Martinez-Marti, Juan David Assaf-Pastrana, Enriqueta Felip, and Pilar Garrido. Current state-of-the-art therapy for malignant pleural mesothelioma and future options centered on immunotherapy. Cancers, 15:5787, Dec 2023. URL: https://doi.org/10.3390/cancers15245787, doi:10.3390/cancers15245787. This article has 11 citations.

  4. (chiec2024immunotherapyfortreatment pages 1-2): Lauren Chiec and Debora S. Bruno. Immunotherapy for treatment of pleural mesothelioma: current and emerging therapeutic strategies. International Journal of Molecular Sciences, 25:10861, Oct 2024. URL: https://doi.org/10.3390/ijms251910861, doi:10.3390/ijms251910861. This article has 8 citations.

  5. (jain2024malignantpleuralmesothelioma pages 1-2): Molly Jain, Morgan Kay Crites, Patricia Rich, and Bharat Bajantri. Malignant pleural mesothelioma: a comprehensive review. Journal of Clinical Medicine, 13:5837, Sep 2024. URL: https://doi.org/10.3390/jcm13195837, doi:10.3390/jcm13195837. This article has 30 citations.

  6. (lewandowska2024diagnosisandtreatment pages 1-2): Zofia Lewandowska and Dariusz M. Kowalski. Diagnosis and treatment of pleural mesothelioma. state of the art 2024. Oncology in Clinical Practice, Oct 2024. URL: https://doi.org/10.5603/ocp.100725, doi:10.5603/ocp.100725. This article has 1 citations.

  7. (kindler2025treatmentofpleural pages 2-3): MD Hedy L. Kindler, M. M. No fi sat Ismaila, MD Lyudmila Bazhenova, MD Quincy Chu, MD Jane E. Churpek, MD Ibiayi Dagogo-Jack, MD Darren S. Bryan, MD PhD Michael W. Drazer, MD Patrick Forde, MD Aliya N. Husain, MD Jennifer L. Sauter, MD Valerie Rusch, MB BCh Penelope A. Bradbury, MD PhD B.C. John Cho, MD MSc Marc de Perrot, MD Azam Ghafoor, MD David L. Graham, MD PhD Ola Khorshid, MS Cgc Alexandra Lebensohn, Bsn RN Ocn Julie White, and MD Raf fi t Hassan. Treatment of pleural mesothelioma: asco guideline update. Journal of Clinical Oncology, 43:1006-1038, Jan 2025. URL: https://doi.org/10.1200/jco-24-02425, doi:10.1200/jco-24-02425. This article has 58 citations and is from a highest quality peer-reviewed journal.

  8. (bertin2023thecurrenttreatment pages 1-2): Beatriz Bertin, Miguel Zugman, and Gustavo Schvartsman. The current treatment landscape of malignant pleural mesothelioma and future directions. Cancers, 15:5808, Dec 2023. URL: https://doi.org/10.3390/cancers15245808, doi:10.3390/cancers15245808. This article has 18 citations.

  9. (OpenTargets Search: malignant mesothelioma,malignant pleural mesothelioma): Open Targets Query (malignant mesothelioma,malignant pleural mesothelioma, 39 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  10. (tyagi2024germlinebap1mutation pages 14-17): G Tyagi. Germline bap1 mutation alter the tumor immune microenvironment and impact the progression of malignant mesothelioma (mm). Unknown journal, 2024.

  11. (tyagi2024germlinebap1mutation pages 11-14): G Tyagi. Germline bap1 mutation alter the tumor immune microenvironment and impact the progression of malignant mesothelioma (mm). Unknown journal, 2024.

  12. (kindler2025treatmentofpleural pages 3-5): MD Hedy L. Kindler, M. M. No fi sat Ismaila, MD Lyudmila Bazhenova, MD Quincy Chu, MD Jane E. Churpek, MD Ibiayi Dagogo-Jack, MD Darren S. Bryan, MD PhD Michael W. Drazer, MD Patrick Forde, MD Aliya N. Husain, MD Jennifer L. Sauter, MD Valerie Rusch, MB BCh Penelope A. Bradbury, MD PhD B.C. John Cho, MD MSc Marc de Perrot, MD Azam Ghafoor, MD David L. Graham, MD PhD Ola Khorshid, MS Cgc Alexandra Lebensohn, Bsn RN Ocn Julie White, and MD Raf fi t Hassan. Treatment of pleural mesothelioma: asco guideline update. Journal of Clinical Oncology, 43:1006-1038, Jan 2025. URL: https://doi.org/10.1200/jco-24-02425, doi:10.1200/jco-24-02425. This article has 58 citations and is from a highest quality peer-reviewed journal.

  13. (zahiu2025molecularinsightsinto pages 17-19): Teodora Zahiu, Carmen Mihaela Mihu, Bianca A. Bosca, Mariana Mărginean, Lavinia Patricia Mocan, Roxana-Adelina Ștefan, Rada Teodora Suflețel, Carina Mihu, and Carmen Stanca Melincovici. Molecular insights into pleural mesothelioma: unveiling pathogenic mechanisms and therapeutic opportunities. Diagnostics, 15:1323, May 2025. URL: https://doi.org/10.3390/diagnostics15111323, doi:10.3390/diagnostics15111323. This article has 4 citations.

  14. (kindler2025treatmentofpleural media fd734332): MD Hedy L. Kindler, M. M. No fi sat Ismaila, MD Lyudmila Bazhenova, MD Quincy Chu, MD Jane E. Churpek, MD Ibiayi Dagogo-Jack, MD Darren S. Bryan, MD PhD Michael W. Drazer, MD Patrick Forde, MD Aliya N. Husain, MD Jennifer L. Sauter, MD Valerie Rusch, MB BCh Penelope A. Bradbury, MD PhD B.C. John Cho, MD MSc Marc de Perrot, MD Azam Ghafoor, MD David L. Graham, MD PhD Ola Khorshid, MS Cgc Alexandra Lebensohn, Bsn RN Ocn Julie White, and MD Raf fi t Hassan. Treatment of pleural mesothelioma: asco guideline update. Journal of Clinical Oncology, 43:1006-1038, Jan 2025. URL: https://doi.org/10.1200/jco-24-02425, doi:10.1200/jco-24-02425. This article has 58 citations and is from a highest quality peer-reviewed journal.

  15. (kindler2025treatmentofpleural media c1e908f8): MD Hedy L. Kindler, M. M. No fi sat Ismaila, MD Lyudmila Bazhenova, MD Quincy Chu, MD Jane E. Churpek, MD Ibiayi Dagogo-Jack, MD Darren S. Bryan, MD PhD Michael W. Drazer, MD Patrick Forde, MD Aliya N. Husain, MD Jennifer L. Sauter, MD Valerie Rusch, MB BCh Penelope A. Bradbury, MD PhD B.C. John Cho, MD MSc Marc de Perrot, MD Azam Ghafoor, MD David L. Graham, MD PhD Ola Khorshid, MS Cgc Alexandra Lebensohn, Bsn RN Ocn Julie White, and MD Raf fi t Hassan. Treatment of pleural mesothelioma: asco guideline update. Journal of Clinical Oncology, 43:1006-1038, Jan 2025. URL: https://doi.org/10.1200/jco-24-02425, doi:10.1200/jco-24-02425. This article has 58 citations and is from a highest quality peer-reviewed journal.

  16. (kindler2025treatmentofpleural media 9d842ba2): MD Hedy L. Kindler, M. M. No fi sat Ismaila, MD Lyudmila Bazhenova, MD Quincy Chu, MD Jane E. Churpek, MD Ibiayi Dagogo-Jack, MD Darren S. Bryan, MD PhD Michael W. Drazer, MD Patrick Forde, MD Aliya N. Husain, MD Jennifer L. Sauter, MD Valerie Rusch, MB BCh Penelope A. Bradbury, MD PhD B.C. John Cho, MD MSc Marc de Perrot, MD Azam Ghafoor, MD David L. Graham, MD PhD Ola Khorshid, MS Cgc Alexandra Lebensohn, Bsn RN Ocn Julie White, and MD Raf fi t Hassan. Treatment of pleural mesothelioma: asco guideline update. Journal of Clinical Oncology, 43:1006-1038, Jan 2025. URL: https://doi.org/10.1200/jco-24-02425, doi:10.1200/jco-24-02425. This article has 58 citations and is from a highest quality peer-reviewed journal.

  17. (kindler2025treatmentofpleural media 39f509f9): MD Hedy L. Kindler, M. M. No fi sat Ismaila, MD Lyudmila Bazhenova, MD Quincy Chu, MD Jane E. Churpek, MD Ibiayi Dagogo-Jack, MD Darren S. Bryan, MD PhD Michael W. Drazer, MD Patrick Forde, MD Aliya N. Husain, MD Jennifer L. Sauter, MD Valerie Rusch, MB BCh Penelope A. Bradbury, MD PhD B.C. John Cho, MD MSc Marc de Perrot, MD Azam Ghafoor, MD David L. Graham, MD PhD Ola Khorshid, MS Cgc Alexandra Lebensohn, Bsn RN Ocn Julie White, and MD Raf fi t Hassan. Treatment of pleural mesothelioma: asco guideline update. Journal of Clinical Oncology, 43:1006-1038, Jan 2025. URL: https://doi.org/10.1200/jco-24-02425, doi:10.1200/jco-24-02425. This article has 58 citations and is from a highest quality peer-reviewed journal.

  18. (kindler2025treatmentofpleural media 0889009a): MD Hedy L. Kindler, M. M. No fi sat Ismaila, MD Lyudmila Bazhenova, MD Quincy Chu, MD Jane E. Churpek, MD Ibiayi Dagogo-Jack, MD Darren S. Bryan, MD PhD Michael W. Drazer, MD Patrick Forde, MD Aliya N. Husain, MD Jennifer L. Sauter, MD Valerie Rusch, MB BCh Penelope A. Bradbury, MD PhD B.C. John Cho, MD MSc Marc de Perrot, MD Azam Ghafoor, MD David L. Graham, MD PhD Ola Khorshid, MS Cgc Alexandra Lebensohn, Bsn RN Ocn Julie White, and MD Raf fi t Hassan. Treatment of pleural mesothelioma: asco guideline update. Journal of Clinical Oncology, 43:1006-1038, Jan 2025. URL: https://doi.org/10.1200/jco-24-02425, doi:10.1200/jco-24-02425. This article has 58 citations and is from a highest quality peer-reviewed journal.

  19. (NCT02899299 chunk 1): Study of Nivolumab Combined With Ipilimumab Versus Pemetrexed and Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma Patients. Bristol-Myers Squibb. 2016. ClinicalTrials.gov Identifier: NCT02899299

  20. (cecchi2025perioperativetreatmentsin pages 9-10): Luigi Giovanni Cecchi, Marta Aliprandi, Fabio De Vincenzo, Matteo Perrino, Nadia Cordua, Federica Borea, Alessandro Bertocchi, Antonio Federico, Giuseppe Marulli, Armando Santoro, Giovanni Luca Ceresoli, and Paolo Andrea Zucali. Perioperative treatments in pleural mesothelioma: state of the art and future directions. Cancers, 17:3199, Sep 2025. URL: https://doi.org/10.3390/cancers17193199, doi:10.3390/cancers17193199. This article has 4 citations.