RET fusion-positive thyroid cancer is a molecularly-defined subset of papillary thyroid carcinoma (PTC) harboring chromosomal rearrangements involving the RET proto-oncogene. These fusions occur in approximately 10-20% of papillary thyroid cancers and are particularly enriched in radiation-induced thyroid cancer. The RET kinase domain is fused to various partners that provide dimerization domains, leading to constitutive receptor activation. Unlike RET point mutations in medullary thyroid cancer, RET fusions arise in thyroid follicular cells and cause papillary histology. Highly selective RET inhibitors selpercatinib and pralsetinib provide effective targeted therapy for RET fusion-positive thyroid cancer.
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name: RET Fusion-Positive Thyroid Cancer
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-04-22T20:13:21Z'
description: >-
RET fusion-positive thyroid cancer is a molecularly-defined subset of papillary
thyroid carcinoma (PTC) harboring chromosomal rearrangements involving the RET
proto-oncogene. These fusions occur in approximately 10-20% of papillary thyroid
cancers and are particularly enriched in radiation-induced thyroid cancer. The
RET kinase domain is fused to various partners that provide dimerization domains,
leading to constitutive receptor activation. Unlike RET point mutations in medullary
thyroid cancer, RET fusions arise in thyroid follicular cells and cause papillary
histology. Highly selective RET inhibitors selpercatinib and pralsetinib provide
effective targeted therapy for RET fusion-positive thyroid cancer.
categories:
- Endocrine Cancer
- Molecularly-Defined Cancer
parents:
- thyroid carcinoma
has_subtypes:
- name: RET/PTC1 (CCDC6-RET)
description: >-
Most common RET rearrangement in sporadic papillary thyroid cancer,
accounting for approximately 60% of RET fusions. The CCDC6 partner
provides a coiled-coil dimerization domain.
- name: RET/PTC3 (NCOA4-RET)
description: >-
Second most common RET rearrangement, particularly associated with
radiation-induced thyroid cancer (Chernobyl). Often associated with
solid variant PTC histology.
- name: Other RET Fusions
description: >-
Multiple other fusion partners have been identified including PRKAR1A,
TRIM24, and others. All result in constitutive RET activation.
pathophysiology:
- name: RET Fusion and Constitutive Kinase Activation
description: >-
Chromosomal rearrangements fuse the RET tyrosine kinase domain with
upstream partners that provide dimerization domains. This creates
constitutively active chimeric proteins that signal independently of
RET ligands (GDNF family members).
cell_types:
- preferred_term: thyroid follicular cell
term:
id: CL:0002258
label: thyroid follicular cell
biological_processes:
- preferred_term: receptor signaling protein tyrosine kinase activity
modifier: INCREASED
term:
id: GO:0006468
label: protein phosphorylation
locations:
- preferred_term: thyroid gland
term:
id: UBERON:0002046
label: thyroid gland
downstream:
- target: RAS-MAPK Pathway Activation
description: RET fusion activates RAS-RAF-MEK-ERK signaling cascade
- target: PI3K-AKT Pathway Activation
description: RET fusion stimulates PI3K-AKT survival signaling
- name: RAS-MAPK Pathway Activation
description: >-
Constitutive RET kinase activation drives the RAS-RAF-MEK-ERK signaling
cascade, promoting uncontrolled thyroid follicular cell proliferation.
This is a major effector of RET-mediated thyroid tumorigenesis.
biological_processes:
- preferred_term: MAPK cascade
modifier: INCREASED
term:
id: GO:0000165
label: MAPK cascade
- name: PI3K-AKT Pathway Activation
description: >-
RET activation recruits PI3K and stimulates AKT-mTOR signaling,
promoting cell survival and resistance to apoptosis. Combined with
MAPK activation, this drives thyroid cancer progression.
biological_processes:
- preferred_term: phosphatidylinositol 3-kinase signaling
modifier: INCREASED
term:
id: GO:0043491
label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
histopathology:
- name: Papillary Thyroid Carcinoma
finding_term:
preferred_term: Thyroid Gland Papillary Carcinoma
term:
id: NCIT:C4035
label: Thyroid Gland Papillary Carcinoma
frequency: VERY_FREQUENT
description: Papillary thyroid carcinomas are the most common thyroid cancers.
evidence:
- reference: PMID:21221869
reference_title: "Papillary thyroid carcinoma variants."
supports: PARTIAL
snippet: "Papillary thyroid carcinomas are the most common thyroid cancers"
explanation: Abstract notes papillary thyroid carcinoma as the most common thyroid cancer.
phenotypes:
- category: Endocrine
name: Thyroid Nodule
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Patients typically present with a thyroid nodule. RET fusion-positive
PTCs may present at younger ages, particularly in radiation-associated
cases.
phenotype_term:
preferred_term: Thyroid carcinoma
term:
id: HP:0002890
label: Thyroid carcinoma
- category: Systemic
name: Cervical Lymphadenopathy
frequency: FREQUENT
description: >-
Cervical lymph node metastases are common at presentation. RET fusion-
positive PTCs tend to have favorable overall prognosis despite lymph
node involvement.
phenotype_term:
preferred_term: Lymphadenopathy
term:
id: HP:0002716
label: Lymphadenopathy
- category: Constitutional
name: Fatigue
frequency: OCCASIONAL
description: >-
Constitutional symptoms are uncommon at diagnosis but may occur with
advanced metastatic disease.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
biochemical:
- name: Thyroglobulin
notes: >-
Serum thyroglobulin is the primary tumor marker for monitoring
differentiated thyroid cancer after thyroidectomy. RET fusion-positive
tumors generally maintain differentiation and thyroglobulin expression.
- name: RET Fusion Testing
notes: >-
RET fusions can be detected by FISH, RT-PCR, or next-generation
sequencing (RNA-based NGS preferred). Testing is indicated for
radioiodine-refractory disease.
genetic:
- name: RET
association: Somatic Gene Fusions
notes: >-
RET fusions occur in 10-20% of papillary thyroid cancers. Common fusion
partners include CCDC6 (RET/PTC1) and NCOA4 (RET/PTC3). Particularly
enriched in radiation-induced thyroid cancer. Targetable with selective
RET inhibitors.
evidence:
- reference: PMID:39502057
reference_title: "[Correlations of Ultrasound Features With Gene Mutations and Pathologic Subtypes in Papillary Thyroid Carcinoma]."
supports: PARTIAL
snippet: "The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations."
explanation: "Supports RET/PTC rearrangements as common mutations in papillary thyroid carcinoma."
treatments:
- name: Thyroidectomy
description: >-
Total thyroidectomy with lymph node dissection is the primary treatment.
Most RET fusion-positive PTCs have excellent outcomes with surgery alone.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Radioiodine Therapy
description: >-
Adjuvant radioactive iodine therapy is used for intermediate and high-risk
disease. RET fusion-positive tumors generally maintain radioiodine avidity
better than BRAF-mutant tumors.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
- name: Selpercatinib
description: >-
Highly selective RET inhibitor approved for RET fusion-positive thyroid
cancer that is radioiodine-refractory. Demonstrates high response rates
with durable disease control.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: selpercatinib
term:
id: NCIT:C134987
label: Selpercatinib
- name: Pralsetinib
description: >-
Another selective RET inhibitor with activity in RET fusion-positive
thyroid cancer. Similar efficacy profile to selpercatinib.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: pralsetinib
term:
id: NCIT:C132295
label: Pralsetinib
- name: Lenvatinib or Sorafenib
description: >-
Multi-kinase inhibitors approved for radioiodine-refractory differentiated
thyroid cancer. May be used but selective RET inhibitors are preferred
for RET fusion-positive tumors.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: lenvatinib
term:
id: CHEBI:85994
label: lenvatinib
disease_term:
preferred_term: papillary thyroid carcinoma
term:
id: MONDO:0005075
label: thyroid gland papillary carcinoma
classifications:
icdo_morphology:
classification_value: Carcinoma
harrisons_chapter:
- classification_value: cancer
- classification_value: solid tumor
references:
- reference: DOI:10.1007/s40265-024-02040-5
title: 'RET Inhibitors in RET Fusion-Positive Lung Cancers: Past, Present, and Future'
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: 'RET Inhibitors in RET Fusion-Positive Lung Cancers: Past, Present, and Future'
supporting_text: 'RET Inhibitors in RET Fusion-Positive Lung Cancers: Past, Present, and Future'
- reference: DOI:10.1038/s41698-023-00347-2
title: Genomic landscape of 891 RET fusions detected across diverse solid tumor types
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: In this study, we report the clinicopathologic and genomic profiles of 891 patients with RET fusion driven advanced solid tumors.
supporting_text: In this study, we report the clinicopathologic and genomic profiles of 891 patients with RET fusion driven advanced solid tumors.
evidence:
- reference: DOI:10.1038/s41698-023-00347-2
reference_title: Genomic landscape of 891 RET fusions detected across diverse solid tumor types
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: In this study, we report the clinicopathologic and genomic profiles of 891 patients with RET fusion driven advanced solid tumors.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.1158/1078-0432.ccr-23-0459
title: 'FDA Approval Summary: Selpercatinib for the Treatment of Advanced <i>RET</i> Fusion-Positive Solid Tumors'
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: 'FDA Approval Summary: Selpercatinib for the Treatment of Advanced <i>RET</i> Fusion-Positive Solid Tumors'
supporting_text: On September 21, 2022, the FDA granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for the treatment of adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.
evidence:
- reference: DOI:10.1158/1078-0432.ccr-23-0459
reference_title: 'FDA Approval Summary: Selpercatinib for the Treatment of Advanced <i>RET</i> Fusion-Positive Solid Tumors'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: On September 21, 2022, the FDA granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for the treatment of adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.1186/s12885-023-10852-z
title: Highly sensitive droplet digital PCR for detection of RET fusion in papillary thyroid cancer
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: Thyroid cancer is the most frequent malignancy of the endocrine system, of which papillary thyroid cancer (PTC) is the predominant form with a rapid increasing incidence worldwide.
supporting_text: Thyroid cancer is the most frequent malignancy of the endocrine system, of which papillary thyroid cancer (PTC) is the predominant form with a rapid increasing incidence worldwide.
evidence:
- reference: DOI:10.1186/s12885-023-10852-z
reference_title: Highly sensitive droplet digital PCR for detection of RET fusion in papillary thyroid cancer
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Thyroid cancer is the most frequent malignancy of the endocrine system, of which papillary thyroid cancer (PTC) is the predominant form with a rapid increasing incidence worldwide.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.1186/s42047-024-00157-1
title: Predictive biomarkers in thyroid cancer in the current molecular-morphology paradigm
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: Thyroid cancer is one of the most common types of cancer worldwide.
supporting_text: Thyroid cancer is one of the most common types of cancer worldwide.
evidence:
- reference: DOI:10.1186/s42047-024-00157-1
reference_title: Predictive biomarkers in thyroid cancer in the current molecular-morphology paradigm
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Thyroid cancer is one of the most common types of cancer worldwide.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.1200/jco.23.02503
title: 'Durability of Response With Selpercatinib in Patients With <i>RET</i>-Activated Thyroid Cancer: Long-Term Safety and Efficacy From LIBRETTO-001'
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: Clinical trials frequently include multiple end points that mature at different times.
supporting_text: Clinical trials frequently include multiple end points that mature at different times.
evidence:
- reference: DOI:10.1200/jco.23.02503
reference_title: 'Durability of Response With Selpercatinib in Patients With <i>RET</i>-Activated Thyroid Cancer: Long-Term Safety and Efficacy From LIBRETTO-001'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Clinical trials frequently include multiple end points that mature at different times.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.1245/s10434-024-15500-9
title: 'Defining the Genomic Landscape of Diffuse Sclerosing Papillary Thyroid Carcinoma: Prognostic Implications of RET Fusions'
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: 'Defining the Genomic Landscape of Diffuse Sclerosing Papillary Thyroid Carcinoma: Prognostic Implications of RET Fusions'
supporting_text: 'Defining the Genomic Landscape of Diffuse Sclerosing Papillary Thyroid Carcinoma: Prognostic Implications of RET Fusions'
- reference: DOI:10.1530/erc-23-0117
title: 'RET fusion genes in pediatric and adult thyroid carcinomas: cohort characteristics and prognosis'
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes.
supporting_text: Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes.
evidence:
- reference: DOI:10.1530/erc-23-0117
reference_title: 'RET fusion genes in pediatric and adult thyroid carcinomas: cohort characteristics and prognosis'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.3389/fendo.2024.1346476
title: Systemic treatments for radioiodine-refractory thyroid cancers
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: Differentiated thyroid cancers (DTCs) constitute the primary histological subtype within thyroid cancer.
supporting_text: Differentiated thyroid cancers (DTCs) constitute the primary histological subtype within thyroid cancer.
evidence:
- reference: DOI:10.3389/fendo.2024.1346476
reference_title: Systemic treatments for radioiodine-refractory thyroid cancers
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Differentiated thyroid cancers (DTCs) constitute the primary histological subtype within thyroid cancer.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.3389/pore.2023.1611138
title: RET rearrangements are relevant to histopathologic subtypes and clinicopathological features in Thai papillary thyroid carcinoma patients
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer.
supporting_text: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer.
evidence:
- reference: DOI:10.3389/pore.2023.1611138
reference_title: RET rearrangements are relevant to histopathologic subtypes and clinicopathological features in Thai papillary thyroid carcinoma patients
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.3390/cancers15133394
title: The Difference in Clinical Behavior of Gene Fusions Involving RET/PTC Fusions and THADA/IGF2BP3 Fusions in Thyroid Nodules
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules.
supporting_text: Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules.
evidence:
- reference: DOI:10.3390/cancers15133394
reference_title: The Difference in Clinical Behavior of Gene Fusions Involving RET/PTC Fusions and THADA/IGF2BP3 Fusions in Thyroid Nodules
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.3390/cancers15164146
title: RET-Altered Cancers—A Tumor-Agnostic Review of Biology, Diagnosis and Targeted Therapy Activity
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: RET alterations, such as fusions or mutations, drive the growth of multiple tumor types.
supporting_text: RET alterations, such as fusions or mutations, drive the growth of multiple tumor types.
evidence:
- reference: DOI:10.3390/cancers15164146
reference_title: RET-Altered Cancers—A Tumor-Agnostic Review of Biology, Diagnosis and Targeted Therapy Activity
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: RET alterations, such as fusions or mutations, drive the growth of multiple tumor types.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.3390/cancers16010031
title: 'Selective RET Inhibitors (SRIs) in Cancer: A Journey from Multi-Kinase Inhibitors to the Next Generation of SRIs'
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: RET is a receptor tyrosine kinase that plays an important role in the development of neurons and kidneys.
supporting_text: RET is a receptor tyrosine kinase that plays an important role in the development of neurons and kidneys.
evidence:
- reference: DOI:10.3390/cancers16010031
reference_title: 'Selective RET Inhibitors (SRIs) in Cancer: A Journey from Multi-Kinase Inhibitors to the Next Generation of SRIs'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: RET is a receptor tyrosine kinase that plays an important role in the development of neurons and kidneys.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.3390/cancers16162877
title: 'Non-Small-Cell Lung Cancers (NSCLCs) Harboring RET Gene Fusion, from Their Discovery to the Advent of New Selective Potent RET Inhibitors: “Shadows and Fogs”'
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: RET fusions are relatively rare in Non-Small-Cell Lung Cancers (NSCLCs), being around 1–2% of all NSCLCs.
supporting_text: RET fusions are relatively rare in Non-Small-Cell Lung Cancers (NSCLCs), being around 1–2% of all NSCLCs.
evidence:
- reference: DOI:10.3390/cancers16162877
reference_title: 'Non-Small-Cell Lung Cancers (NSCLCs) Harboring RET Gene Fusion, from Their Discovery to the Advent of New Selective Potent RET Inhibitors: “Shadows and Fogs”'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: RET fusions are relatively rare in Non-Small-Cell Lung Cancers (NSCLCs), being around 1–2% of all NSCLCs.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
- reference: DOI:10.3390/genes14071314
title: 'Update on Molecular Diagnostics in Thyroid Pathology: A Review'
found_in:
- RET_Fusion_Thyroid_Cancer-deep-research-falcon.md
findings:
- statement: Thyroid nodules are quite common, and the determination of a nodule of concern is complex, involving serum testing, radiology and, in some cases, pathological evaluation.
supporting_text: Thyroid nodules are quite common, and the determination of a nodule of concern is complex, involving serum testing, radiology and, in some cases, pathological evaluation.
evidence:
- reference: DOI:10.3390/genes14071314
reference_title: 'Update on Molecular Diagnostics in Thyroid Pathology: A Review'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Thyroid nodules are quite common, and the determination of a nodule of concern is complex, involving serum testing, radiology and, in some cases, pathological evaluation.
explanation: Deep research cited this publication as relevant literature for RET Fusion Thyroid Cancer.
Target disease: RET fusion‑positive thyroid cancer (molecularly defined subset; most commonly RET fusion‑positive papillary thyroid carcinoma [PTC]) (duke2023fdaapprovalsummary pages 1-3, pekova2023retfusiongenes pages 1-2).
Category: Molecular subtype of differentiated thyroid carcinoma / papillary thyroid carcinoma (duke2023fdaapprovalsummary pages 1-3, pekova2023retfusiongenes pages 1-2).
MONDO ID: A specific MONDO term for “RET fusion‑positive thyroid cancer” was not identified in the retrieved sources; related thyroid cancer MONDO terms exist for other entities (e.g., medullary thyroid gland carcinoma MONDO_0015277, which is typically RET mutation‑driven, not RET fusion‑driven) (parimi2023genomiclandscapeof pages 1-2).
RET fusion‑positive thyroid cancers are thyroid epithelial malignancies driven by oncogenic RET gene rearrangements (RET/PTC). The fusions typically retain the RET kinase domain and use partner‑derived dimerization motifs to enable ligand‑independent RET activation and downstream MAPK/PI3K pathway signaling. RET fusions are enriched in pediatric PTC and in aggressive histologic variants (e.g., diffuse sclerosing PTC), and are associated with high rates of lymph node metastasis and meaningful distant metastasis risk. Clinically, selective RET inhibitors (selpercatinib, pralsetinib) have produced high objective response rates and durable disease control in advanced RET fusion‑positive thyroid cancer, and have become the key real‑world implementation of precision oncology for this subtype (wirth2024durabilityofresponse pages 1-2, clark2023selectiveretinhibitors pages 4-5, pekova2023retfusiongenes pages 1-2).
RET fusion‑positive thyroid cancer refers to thyroid carcinomas harboring in‑frame chromosomal rearrangements involving RET that generate constitutively active RET fusion oncoproteins (duke2023fdaapprovalsummary pages 3-5). These fusions are most commonly observed in papillary thyroid cancer and are rare across most other solid tumors (duke2023fdaapprovalsummary pages 1-3).
Evidence in this report is derived from aggregated disease‑level resources including multi‑institution cohorts, pan‑tumor NGS datasets, clinical trials (LIBRETTO‑001, ARROW), ClinicalTrials.gov trial records, and FDA regulatory reviews (parimi2023genomiclandscapeof pages 1-2, wirth2024durabilityofresponse pages 1-2, duke2023fdaapprovalsummary pages 1-3, NCT03157128 chunk 1).
The primary causal factor is an acquired somatic RET gene fusion (RET rearrangement), which creates an oncogenic fusion protein with constitutive kinase activation (desilets2023retalteredcancers—atumoragnostic pages 2-4, pekova2023retfusiongenes pages 11-12).
Age / pediatric enrichment: In a large cohort (n=993 PTC), RET fusions were detected in 11.4% of PTC overall, and were threefold more frequent in pediatric/adolescent patients (29.8%) than adults (8.7%) (Pekova 2023; published Sep 2023; https://doi.org/10.1530/ERC-23-0117) (pekova2023retfusiongenes pages 1-2).
Radiation exposure: RET/PTC events have been linked to ionizing radiation exposure and radiation‑associated subtypes in thyroid cancer literature (e.g., post‑Chernobyl series and “short radiation latency” associations noted in a 2023 Thai PTC study) (Khonrak 2023; published Apr 2023; https://doi.org/10.3389/pore.2023.1611138) (khonrak2023retrearrangementsare pages 1-2, khonrak2023retrearrangementsare pages 13-13).
No clear protective genetic or environmental factors specific to acquiring RET fusions were identified in the retrieved sources. One cohort cited an association between coexisting chronic lymphocytic thyroiditis and lower recurrence rates in PTC broadly, but this is not a proven protective factor for RET‑fusion initiation (pekova2023retfusiongenes pages 12-13).
The strongest candidate interaction is DNA damage (e.g., radiation) contributing to chromosomal rearrangements that generate RET/PTC fusions, as discussed in the radiation‑associated literature summarized in Thai PTC data and cited post‑Chernobyl series (khonrak2023retrearrangementsare pages 13-13).
RET fusion‑positive thyroid cancer is most often PTC and is frequently associated with aggressive locoregional features.
Aggressive metastatic phenotype (large cohort): In a large Czech cohort of RET fusion‑positive PTC, lymph node metastasis occurred in 75.2% and distant metastasis in 18.6%; metastases were also reported even among microcarcinomas (Pekova 2023; https://doi.org/10.1530/ERC-23-0117) (pekova2023retfusiongenes pages 1-2).
Diffuse sclerosing PTC enrichment and recurrence risk: In diffuse sclerosing PTC (DSPTC), RET fusions were the most common alteration (32% [13/41]), and RET fusion status predicted worse recurrence‑free survival (5‑year RFS 46% vs 84% for other drivers; HR 7.69, p=0.017) (Scholfield 2024; published Jun 2024; https://doi.org/10.1245/s10434-024-15500-9) (scholfield2024definingthegenomic pages 1-3).
Small descriptive cohort: In a retrospective series of operated nodules, RET/PTC fusion‑positive nodules were all malignant (100%) and had a high nodal metastasis rate (80% [4/5]), with 60% diffuse sclerosing variant histology (Tali 2023; published Jun 2023; https://doi.org/10.3390/cancers15133394) (tali2023thedifferencein pages 1-2).
Direct thyroid‑specific QoL metrics for RET fusion‑positive thyroid cancer were not extracted from the retrieved texts. QoL preservation/improvement under selpercatinib was reported across RET‑driven cancers in LIBRETTO‑001, but thyroid‑specific quantitative QoL outcomes were not available in the extracted evidence (wirth2024durabilityofresponse pages 7-7).
The defining alteration is a structural rearrangement (gene fusion) producing an in‑frame RET fusion (RET/PTC). Key fusions retain the RET kinase domain (3′ RET) and incorporate a 5′ partner providing dimerization capability (desilets2023retalteredcancers—atumoragnostic pages 2-4, pekova2023retfusiongenes pages 11-12).
In a large RET fusion‑positive PTC cohort (n=113 RET+ PTCs):
CCDC6::RET: 59.3% (67/113)
NCOA4::RET: 22.1% (25/113)
Other partners included FBXO41, SSBP2, ZMYM2 (Pekova 2023; https://doi.org/10.1530/ERC-23-0117) (pekova2023retfusiongenes pages 3-5).
In a pan‑tumor NGS dataset, thyroid papillary carcinoma had RET fusion prevalence 9.09% (109/1199), and across the overall RET fusion cohort common partners included NCOA4 (32.6%) and CCDC6 (29.9%) (Parimi 2023; published Jan 2023; https://doi.org/10.1038/s41698-023-00347-2) (parimi2023genomiclandscapeof pages 1-2).
RET fusions:
1) retain the RET tyrosine kinase domain in the 3′ fusion portion;
2) are placed under control of a transcriptionally active partner; and
3) often acquire partner‑derived dimerization motifs, enabling ligand‑independent dimerization, phosphorylation, and constitutive signaling (carneiro2024predictivebiomarkersin pages 8-9, desilets2023retalteredcancers—atumoragnostic pages 2-4).
Downstream pathways include MAPK‑ERK, PI3K‑AKT, and JAK‑STAT signaling, supporting proliferative/survival programs (carneiro2024predictivebiomarkersin pages 8-9, chen2024retinhibitorsin pages 1-3).
Ionizing radiation exposure has a longstanding association with RET/PTC rearrangements (notably pediatric and post‑radiation clusters), summarized in contemporary PTC literature and referenced in 2023 Thai PTC analysis (khonrak2023retrearrangementsare pages 1-2, khonrak2023retrearrangementsare pages 13-13).
No specific lifestyle or infectious etiologies were identified in the retrieved sources.
Trigger/event: Somatic chromosomal rearrangement generating an in‑frame RET fusion (RET/PTC).
Upstream mechanism: Fusion retains the RET kinase domain and partner‑derived interaction motifs → ligand‑independent dimerization and RET autophosphorylation (desilets2023retalteredcancers—atumoragnostic pages 2-4, pekova2023retfusiongenes pages 11-12).
Downstream signaling: Activation of MAPK‑ERK and PI3K‑AKT (and JAK‑STAT) cascades promotes proliferation, survival, migration, and oncogenic transformation (carneiro2024predictivebiomarkersin pages 8-9, chen2024retinhibitorsin pages 1-3).
Clinical phenotype: Higher probability of nodal metastasis and clinically aggressive variants (DSPTC association), with high disease‑specific survival in intensively treated cohorts but higher recurrence risk in certain subtypes (scholfield2024definingthegenomic pages 1-3, pekova2023retfusiongenes pages 1-2).
Evidence linking RET alterations to immune microenvironment changes in PTC exists (RET variation associated with immune infiltration patterns), but this was not specific to RET fusions and is not used here as defining evidence for RET fusion‑positive disease (pekova2023retfusiongenes pages 1-2).
Comprehensive multi‑omics signatures specific to RET fusion‑positive thyroid cancer were not extracted in the available sources.
RET fusion‑positive PTC is enriched in younger patients, including pediatric and adolescent presentations (pekova2023retfusiongenes pages 1-2, khonrak2023retrearrangementsare pages 1-2).
In a large cohort, metastases (nodal and distant) were frequent, but “true recurrences” were rare (2.4%, adults only) and disease‑specific survival remained high (10‑year 95%) (pekova2023retfusiongenes pages 1-2). In DSPTC, RET fusions identified a higher recurrence‑risk subgroup (5‑year RFS 46%) (scholfield2024definingthegenomic pages 1-3).
RET fusions are most commonly found in PTC.
Reported prevalence ranges (study‑dependent):
* FDA review: RET fusions are observed most commonly in papillary thyroid cancer (5–10%) (Duke 2023; published Sep 15, 2023; https://doi.org/10.1158/1078-0432.CCR-23-0459) (duke2023fdaapprovalsummary pages 1-3).
DNA‑NGS cohort: thyroid papillary carcinoma RET fusion prevalence 9.09% (109/1199) (Parimi 2023; Jan 2023; https://doi.org/10.1038/s41698-023-00347-2) (parimi2023genomiclandscapeof pages 1-2).
Czech cohort: RET fusions 11.4% (113/993) of PTC; 29.8% pediatric/adolescent vs 8.7% adult (Pekova 2023; Sep 2023; https://doi.org/10.1530/ERC-23-0117) (pekova2023retfusiongenes pages 1-2).
RET fusions in thyroid cancer are generally somatic driver events rather than inherited. (Germline RET alterations are relevant to MEN2 and medullary thyroid carcinoma, not the RET‑fusion PTC subtype.) (alzumaili2023updateonmolecular pages 5-7).
Preferred approach: Comprehensive NGS, ideally including DNA and RNA interrogation for fusions, is emphasized as the best method to identify RET fusions and concomitant alterations (desilets2023retalteredcancers—atumoragnostic pages 1-2, desilets2023retalteredcancers—atumoragnostic pages 8-9).
Alternatives/adjuncts: RT‑PCR and FISH may be used when NGS is unavailable, with known limitations (partner dependence, inability to identify partners/breakpoints for FISH) (desilets2023retalteredcancers—atumoragnostic pages 8-9, chen2024retinhibitorsin pages 3-5).
IHC: Sensitivity/specificity for RET IHC reported as 87%/82%, but performance is partner dependent and it is “not recommended as a clinical screening assay for oncogenic RET alterations” (desilets2023retalteredcancers—atumoragnostic pages 8-9).
FISH: Break‑apart FISH sensitivity is fusion‑partner dependent; in one series, thyroid cancer sensitivity was 88%, and partner‑specific sensitivity examples included 100% for KIF5B/CCDC6 but 67% for NCOA4 (desilets2023retalteredcancers—atumoragnostic pages 8-9).
ddPCR (CCDC6::RET): ddPCR improved analytical sensitivity over qRT‑PCR with LoD 128.0 copies/reaction vs 430.7 copies/reaction; in 112 clinical PTC samples ddPCR detected 13.4% (15/112) positives vs 9.8% (11/112) by qRT‑PCR (Chen 2023; Apr 2023; https://doi.org/10.1186/s12885-023-10852-z) (chen2023highlysensitivedroplet pages 1-2, chen2023highlysensitivedroplet pages 2-4).
Commercial thyroid nodule platforms: ThyroSeq v3 (DNA+RNA panel) reports overall performance for nodule classification of 94% sensitivity, 89% specificity, 92% accuracy, and includes RET fusions; Afirma XA uses whole‑transcriptome RNA sequencing and enumerates fusions including CCDC6::RET and NCOA4::RET (Alzumaili 2023; Jun 2023; https://doi.org/10.3390/genes14071314) (alzumaili2023updateonmolecular pages 5-7).
RET fusions overlap with other fusion‑driven thyroid cancers (e.g., NTRK fusions) and mutation‑driven PTC (BRAF, RAS). Molecular testing distinguishes these entities for targeted therapy selection (alzumaili2023updateonmolecular pages 5-7, pekova2023retfusiongenes pages 1-2).
Disease‑specific survival (large cohort): In RET fusion‑positive PTC, 2‑, 5‑, 10‑year disease‑specific survival were 99%, 96%, 95%, despite high metastatic burden, suggesting aggressive biology but potentially favorable survival with intensive multimodal management (pekova2023retfusiongenes pages 1-2).
Subtype‑specific recurrence risk: In DSPTC, RET fusions predicted worse recurrence‑free survival (5‑year RFS 46%) and were the only independent recurrence predictor (HR 7.69) (scholfield2024definingthegenomic pages 1-3).
Regulatory indication (FDA): FDA accelerated approval (May 8, 2020) includes adult and pediatric (≥12 years) patients with advanced/metastatic RET fusion‑positive thyroid cancer requiring systemic therapy and RAI‑refractory (if RAI appropriate) (Duke 2023; https://doi.org/10.1158/1078-0432.CCR-23-0459) (duke2023fdaapprovalsummary pages 1-3).
Dose concept (FDA review): 120 mg orally BID if <50 kg; 160 mg orally BID if ≥50 kg (duke2023fdaapprovalsummary pages 3-5).
Efficacy (LIBRETTO‑001 long‑term update): At January 2023 cutoff, RET fusion‑positive thyroid cancer cohort (n=66) demonstrated:
ORR 95.8% in treatment‑naïve patients (n=24) and 85.4% in previously treated patients (n=41) (Wirth 2024; published Sep 2024; https://doi.org/10.1200/JCO.23.02503) (wirth2024durabilityofresponse pages 7-7).
Median PFS: not reached (treatment‑naïve) and 27.4 months (pretreated) (wirth2024durabilityofresponse pages 1-2, wirth2024durabilityofresponse pages 7-7).
ARROW trial efficacy (previously treated RET fusion+ thyroid cancer): ORR 90.9% (95% CI 70.8–98.9) in 22 previously treated patients (review summary; Chen 2024; published Oct 2024; https://doi.org/10.3389/fendo.2024.1346476) (chen2024systemictreatmentsfor pages 7-8).
Another synthesis reports ORR 89% (95% CI 52–100) in RET fusion‑positive thyroid cancer cohorts (Clark 2023; published Dec 2023; https://doi.org/10.3390/cancers16010031) (clark2023selectiveretinhibitors pages 4-5).
Key toxicities (grade ≥3 TRAEs, thyroid cancer population in summary): hypertension 17%, neutropenia 13%, lymphopenia 12%, anemia 10%; pneumonitis 4%; discontinuation 4%; treatment‑related death 1% (clark2023selectiveretinhibitors pages 4-5).
Acquired resistance to selective RET inhibitors may involve:
* On‑target RET mutations, especially solvent‑front RET G810 substitutions (G810X); also RET L730V/I, Y806, V738 alterations (desilets2023retalteredcancers—atumoragnostic pages 15-16).
Bypass mechanisms, including MET amplification and MAPK reactivation via emergent KRAS/NRAS/BRAF* alterations (desilets2023retalteredcancers—atumoragnostic pages 15-16).
Next‑generation RET inhibitors are being developed with activity against solvent‑front and gatekeeper mutants (e.g., preclinical development described in 2023 review; APS03118 potency against G810 and V804 mutants, with PDX/intracranial models) (clark2023selectiveretinhibitors pages 9-11).
The CHEBI IDs for selpercatinib and pralsetinib were not retrieved in the available sources.
Primary prevention for RET fusion acquisition is not established. Secondary prevention consists of early detection and appropriate molecular testing to enable precision therapy. Specific screening strategies for RET fusions in the general population are not described in the retrieved sources.
Not identified in retrieved sources.
Selpercatinib preclinical models: FDA review notes selpercatinib activity in in vitro/in vivo models with CCDC6‑RET, KIF5B‑RET, and RET resistance/driver mutations (RET V804M, M918T), and in a mouse intracranial model with a patient‑derived RET fusion‑positive tumor (Duke 2023; https://doi.org/10.1158/1078-0432.CCR-23-0459) (duke2023fdaapprovalsummary pages 3-5).
Engineered resistance models: Engineered Ba/F3 fusion models (e.g., Ba/F3 KIF5B‑RET) and derived resistant lines have been used to characterize on‑target resistance mutations under RET inhibitor pressure (Spitaleri 2024; published Aug 2024; https://doi.org/10.3390/cancers16162877) (spitaleri2024nonsmallcelllungcancers pages 11-12).
PDX and intracranial orthotopic models for next‑gen inhibitors: A 2023 review describes PDX and intracranial orthotopic models including CCDC6‑RET and CCDC6‑RET V804M, demonstrating feasibility of brain‑penetrant next‑generation RET inhibition strategies aimed at resistance (clark2023selectiveretinhibitors pages 9-11).
| Study (first author, year) | Population/cohort | Method | Key findings (with exact numbers) | URL/DOI |
|---|---|---|---|---|
| Parimi, 2023 | Pan-tumor cohort of 891 RET fusion-positive advanced solid tumors; thyroid papillary carcinoma subset | Tissue-based DNA hybrid-capture NGS; subset with liquid biopsy hybrid-capture NGS | RET fusions were most frequent in lung adenocarcinoma and thyroid papillary carcinoma; thyroid papillary carcinoma prevalence was 9.09% (109/1199). In the pan-tumor RET+ cohort, common partners included NCOA4 32.6% and CCDC6 29.9%. Tissue-liquid concordance for RET fusion detection was 100% (8/8) when composite tumor fraction was >1% (parimi2023genomiclandscapeof pages 1-2) | https://doi.org/10.1038/s41698-023-00347-2 |
| Pekova, 2023 | 1,564 thyroid tissue samples including 1,164 carcinomas and 993 PTCs; pediatric and adult patients | Driver testing followed by extensive RET fusion analysis using NGS and real-time PCR | RET fusions were detected exclusively in PTC, in 113/993 (11.4%) patients; prevalence was 29.8% in pediatric/adolescent patients vs 8.7% in adults. 20 RET fusion types were identified. Aggressiveness: lymph node metastasis 75.2%, distant metastasis 18.6%, true recurrences 2.4%. Disease-specific survival: 2-year 99%, 5-year 96%, 10-year 95% (pekova2023retfusiongenes pages 1-2) | https://doi.org/10.1530/ERC-23-0117 |
| Pekova, 2023 | RET fusion-positive PTC subset from the above cohort (n=113) | Targeted RNA sequencing panels with real-time PCR confirmation | Fusion partners: CCDC6 67/113 (59.3%), NCOA4 25/113 (22.1%); additional recurrent/novel partners included FBXO41, SSBP2, ZMYM2. Cohort characteristics: 75.2% female, mean age 32.6 ± 17.4 years, mean tumor size 21.8 ± 12.6 mm (pekova2023retfusiongenes pages 3-5) | https://doi.org/10.1530/ERC-23-0117 |
| Chen, 2023 | TCGA PTC cohort (402) and clinical PTC samples (112) | ddPCR assay for CCDC6::RET vs qRT-PCR; Sanger confirmation | In TCGA, RET fusions were present in 25/402 (6.2%) PTCs; CCDC6::RET accounted for 15/25 (60%) of RET-positive cases. In clinical samples, qRT-PCR detected 11/112 (9.8%) CCDC6::RET-positive cases, while ddPCR detected 15/112 (13.4%), adding 4 extra positives. Limit of detection: 128.0 copies/reaction for ddPCR vs 430.7 copies/reaction for qRT-PCR (chen2023highlysensitivedroplet pages 1-2, chen2023highlysensitivedroplet pages 2-4) | https://doi.org/10.1186/s12885-023-10852-z |
| Khonrak, 2023 | Thai PTC cohort (n=83) | qRT-PCR on FFPE samples for CCDC6::RET and NCOA4::RET | Background prevalence noted as ~10–40% of adult PTC and 45–60% of pediatric/adolescent sporadic PTC; CCDC6 and NCOA4 together account for ~90% of RET::PTC fusions. Phenotype: CCDC6::RET associated with classic subtype and absence of angio/lymphatic invasion; NCOA4::RET associated with tall-cell subtype, angio/lymphatic invasion, and lymph node metastasis (khonrak2023retrearrangementsare pages 1-2) | https://doi.org/10.3389/pore.2023.1611138 |
| Tali, 2023 | Molecularly tested operated thyroid nodules; RET/PTC-positive nodules (n=5) | Retrospective single-center study using preoperative molecular testing and final pathology | All 5/5 (100%) RET/PTC nodules were malignant and Bethesda V/VI. Histology: 60% (3/5) diffuse sclerosing variant, 40% (2/5) classical PTC. Aggressiveness: 80% (4/5) lymph node metastasis, 20% (1/5) extrathyroidal extension; one nodal metastasis case had extranodal spread (tali2023thedifferencein pages 4-6, tali2023thedifferencein pages 1-2) | https://doi.org/10.3390/cancers15133394 |
| Scholfield, 2024 | Diffuse sclerosing papillary thyroid carcinoma (DSPTC) tumors (n=41) | MSK-IMPACT 505-gene panel sequencing | RET fusions were the most common alteration: 32% (13/41). RET fusion-positive tumors occurred at younger age and had more aggressive features and higher T-stage. Outcome: 5-year recurrence-free survival 46% vs 84% for other drivers; multivariable analysis: RET fusion status independent predictor of recurrence (HR 7.69, p=0.017) (scholfield2024definingthegenomic pages 1-3) | https://doi.org/10.1245/s10434-024-15500-9 |
| Selpercatinib (LIBRETTO-001), Wirth, 2024 | RET fusion-positive thyroid cancer in LIBRETTO-001; treatment-naïve (n=24) and pretreated (n=41) | Phase I/II clinical trial long-term update | At January 2023 cutoff, ORR was 95.8% (95% CI 78.9–99.9) in treatment-naïve patients and 85.4% (95% CI 70.8–94.4) in pretreated patients; complete responses 20.8% and 12.2%, respectively. Median follow-up: 24.9 months (naïve) and 30.4 months (pretreated). Median PFS: not reached (naïve) and 27.4 months (pretreated). 3-year PFS 87.3% in treatment-naïve TC; 3-year overall survival 94.4% (naïve) and 65.5% (pretreated) (wirth2024durabilityofresponse pages 1-2, wirth2024durabilityofresponse pages 7-7, wirth2024durabilityofresponse media 08850bf1) | https://doi.org/10.1200/JCO.23.02503 |
| Selpercatinib (regulatory summary), Duke, 2023 | FDA summary referencing prior thyroid approval and broader RET fusion-positive solid tumor activity | FDA review of LIBRETTO-001 | FDA notes RET fusions are seen most commonly in papillary thyroid cancer at 5–10%. For thyroid cancer, prior approval covered adult and pediatric patients ≥12 years with advanced/metastatic RET fusion-positive thyroid cancer requiring systemic therapy and RAI-refractory if RAI appropriate. Selpercatinib activity supported by preclinical models including CCDC6-RET (duke2023fdaapprovalsummary pages 3-5, duke2023fdaapprovalsummary pages 1-3) | https://doi.org/10.1158/1078-0432.CCR-23-0459 |
| Pralsetinib (ARROW), Clark, 2023 | RET fusion-positive thyroid cancer cohort in ARROW (n=20 enrolled; efficacy summarized across thyroid cohorts) | Phase I/II multicohort trial summary | Reported ORR in RET fusion-positive thyroid cancer was 89% (95% CI 52–100). Safety in RET-altered thyroid cancer: grade ≥3 TRAEs included hypertension 17%, neutropenia 13%, lymphopenia 12%, anemia 10%; serious TRAEs in 15%; pneumonitis in 4%; discontinuation due to TRAEs 4%; treatment-related death 1% (clark2023selectiveretinhibitors pages 4-5) | https://doi.org/10.3390/cancers16010031 |
| Pralsetinib (ARROW), Chen, 2024 | Previously treated RET fusion-positive thyroid cancer patients (n=22) | Review summarizing ARROW (NCT03037385) | ORR was 90.9% (95% CI 70.8–98.9) in 22 previously treated RET fusion-positive thyroid cancer patients; review notes FDA approval for RET fusion-positive thyroid cancer in December 2020 (chen2024systemictreatmentsfor pages 7-8) | https://doi.org/10.3389/fendo.2024.1346476 |
| Pralsetinib (ARROW), Desilets, 2023 | Previously treated RET fusion-positive thyroid cancer cohort | Tumor-agnostic review summarizing ARROW | Reported ORR for previously treated RET fusion-positive thyroid cancer was 89%. Common grade 3–4 adverse events across studies included neutropenia 13–31%, hypertension 7–17%, anemia 10–14%, lymphopenia 9–12%, increased creatine phosphokinase 6%, and treatment-emergent pneumonitis 4% (desilets2023retalteredcancers—atumoragnostic pages 13-15) | https://doi.org/10.3390/cancers15164146 |
Table: This table compiles key cohort-level evidence on RET fusion prevalence, dominant fusion partners, clinicopathologic aggressiveness, and selective RET inhibitor outcomes in RET fusion-positive thyroid cancer. It is useful as a compact evidence map for diagnosis, prognosis, and treatment selection.
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(wirth2024durabilityofresponse pages 7-7): Lori J. Wirth, Marcia S. Brose, Vivek Subbiah, Francis Worden, Ben Solomon, Bruce Robinson, Julien Hadoux, Pascale Tomasini, Daniela Weiler, Barbara Deschler-Baier, Daniel S.W. Tan, Patricia Maeda, Yan Lin, Ravinder Singh, Theresa Bayt, Alexander Drilon, and Philippe A. Cassier. Durability of response with selpercatinib in patients with ret-activated thyroid cancer: long-term safety and efficacy from libretto-001. Journal of Clinical Oncology, 42:3187-3195, Sep 2024. URL: https://doi.org/10.1200/jco.23.02503, doi:10.1200/jco.23.02503. This article has 39 citations and is from a highest quality peer-reviewed journal.
(chen2024retinhibitorsin pages 1-3): Monica F. Chen, Matteo Repetto, Clare Wilhelm, and Alexander Drilon. Ret inhibitors in ret fusion-positive lung cancers: past, present, and future. Drugs, 84:1035-1053, Jul 2024. URL: https://doi.org/10.1007/s40265-024-02040-5, doi:10.1007/s40265-024-02040-5. This article has 13 citations and is from a domain leading peer-reviewed journal.
(alzumaili2023updateonmolecular pages 5-7): Bayan Alzumaili and Peter M. Sadow. Update on molecular diagnostics in thyroid pathology: a review. Genes, 14:1314, Jun 2023. URL: https://doi.org/10.3390/genes14071314, doi:10.3390/genes14071314. This article has 40 citations.
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(desilets2023retalteredcancers—atumoragnostic pages 8-9): Antoine Desilets, Matteo Repetto, Soo-Ryum Yang, Eric J. Sherman, and Alexander Drilon. Ret-altered cancers—a tumor-agnostic review of biology, diagnosis and targeted therapy activity. Cancers, 15:4146, Aug 2023. URL: https://doi.org/10.3390/cancers15164146, doi:10.3390/cancers15164146. This article has 41 citations.
(chen2024retinhibitorsin pages 3-5): Monica F. Chen, Matteo Repetto, Clare Wilhelm, and Alexander Drilon. Ret inhibitors in ret fusion-positive lung cancers: past, present, and future. Drugs, 84:1035-1053, Jul 2024. URL: https://doi.org/10.1007/s40265-024-02040-5, doi:10.1007/s40265-024-02040-5. This article has 13 citations and is from a domain leading peer-reviewed journal.
(chen2023highlysensitivedroplet pages 1-2): Meng-ke Chen, Junyu Xue, Ye Sang, Wenting Jiang, Weiman He, Shubin Hong, Weiming Lv, Haipeng Xiao, and Rengyun Liu. Highly sensitive droplet digital pcr for detection of ret fusion in papillary thyroid cancer. BMC Cancer, Apr 2023. URL: https://doi.org/10.1186/s12885-023-10852-z, doi:10.1186/s12885-023-10852-z. This article has 3 citations and is from a peer-reviewed journal.
(chen2023highlysensitivedroplet pages 2-4): Meng-ke Chen, Junyu Xue, Ye Sang, Wenting Jiang, Weiman He, Shubin Hong, Weiming Lv, Haipeng Xiao, and Rengyun Liu. Highly sensitive droplet digital pcr for detection of ret fusion in papillary thyroid cancer. BMC Cancer, Apr 2023. URL: https://doi.org/10.1186/s12885-023-10852-z, doi:10.1186/s12885-023-10852-z. This article has 3 citations and is from a peer-reviewed journal.
(chen2024systemictreatmentsfor pages 7-8): Piaohong Chen, Yu Yao, Huiwen Tan, and Jianwei Li. Systemic treatments for radioiodine-refractory thyroid cancers. Frontiers in Endocrinology, Oct 2024. URL: https://doi.org/10.3389/fendo.2024.1346476, doi:10.3389/fendo.2024.1346476. This article has 15 citations.
(desilets2023retalteredcancers—atumoragnostic pages 15-16): Antoine Desilets, Matteo Repetto, Soo-Ryum Yang, Eric J. Sherman, and Alexander Drilon. Ret-altered cancers—a tumor-agnostic review of biology, diagnosis and targeted therapy activity. Cancers, 15:4146, Aug 2023. URL: https://doi.org/10.3390/cancers15164146, doi:10.3390/cancers15164146. This article has 41 citations.
(clark2023selectiveretinhibitors pages 9-11): Lisa Clark, Geoff Fisher, Sue Brook, Sital Patel, and Hendrik-Tobias Arkenau. Selective ret inhibitors (sris) in cancer: a journey from multi-kinase inhibitors to the next generation of sris. Cancers, 16:31, Dec 2023. URL: https://doi.org/10.3390/cancers16010031, doi:10.3390/cancers16010031. This article has 10 citations.
(spitaleri2024nonsmallcelllungcancers pages 11-12): Gianluca Spitaleri, Pamela Trillo Aliaga, Ilaria Attili, Ester Del Signore, Carla Corvaja, Gloria Pellizzari, Jalissa Katrini, Antonio Passaro, and Filippo de Marinis. Non-small-cell lung cancers (nsclcs) harboring ret gene fusion, from their discovery to the advent of new selective potent ret inhibitors: “shadows and fogs”. Cancers, 16:2877, Aug 2024. URL: https://doi.org/10.3390/cancers16162877, doi:10.3390/cancers16162877. This article has 7 citations.
(wirth2024durabilityofresponse media 08850bf1): Lori J. Wirth, Marcia S. Brose, Vivek Subbiah, Francis Worden, Ben Solomon, Bruce Robinson, Julien Hadoux, Pascale Tomasini, Daniela Weiler, Barbara Deschler-Baier, Daniel S.W. Tan, Patricia Maeda, Yan Lin, Ravinder Singh, Theresa Bayt, Alexander Drilon, and Philippe A. Cassier. Durability of response with selpercatinib in patients with ret-activated thyroid cancer: long-term safety and efficacy from libretto-001. Journal of Clinical Oncology, 42:3187-3195, Sep 2024. URL: https://doi.org/10.1200/jco.23.02503, doi:10.1200/jco.23.02503. This article has 39 citations and is from a highest quality peer-reviewed journal.