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    GENE:

    RET (Ret Proto-Oncogene)

    i
    Other names: RET, Ret Proto-Oncogene, Proto-Oncogene Tyrosine-Protein Kinase Receptor Ret, Cadherin-Related Family Member 16, Rearranged During Transfection, RET Receptor Tyrosine Kinase, Cadherin Family Member 12, Proto-Oncogene C-Ret, CDHF12, CDHR16, PTC, Ret Proto-Oncogene (Multiple Endocrine Neoplasia And Medullary Thyroid Carcinoma 1, Hirschsprung Disease), Multiple Endocrine Neoplasia And Medullary Thyroid Carcinoma 1, Hirschsprung Disease 1, RET-ELE1, HSCR1, MEN2A, MEN2B, RET51, MTC1
    16h
    INCB 84344-102: Safety and Efficacy of Ponatinib for Treatment of Pediatric Recurrent or Refractory Leukemias, Lymphomas or Solid Tumors (clinicaltrials.gov)
    P1/2, N=70, Recruiting, Incyte Biosciences International Sàrl | Trial completion date: Jan 2026 --> Feb 2028 | Trial primary completion date: Jan 2026 --> Feb 2028
    Trial completion date • Trial primary completion date
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    FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • RET (Ret Proto-Oncogene) • FGFR (Fibroblast Growth Factor Receptor) • BLM (BLM RecQ Like Helicase)
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    EGFR mutation • KIT mutation • FGFR mutation • RET mutation
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    Iclusig (ponatinib)
    3d
    Targeted Therapies in Non-Small Cell Lung Cancer: A Contemporary Review. (PubMed, Am J Clin Oncol)
    We outline mechanisms of action, clinical efficacy, and limitations of FDA-approved tyrosine kinase inhibitors (TKIs) and emerging agents, with emphasis on resistance pathways, both on-target and bypass-mediated, observed during treatment with drugs such as osimertinib, crizotinib, sotorasib, and entrectinib. The role of next-generation sequencing (NGS), liquid biopsy, and comprehensive biomarker profiling in guiding personalized therapy selection is also discussed, along with strategies for sequential therapy and rational combination approaches.
    Journal
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
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    BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • HER-2 mutation • ALK rearrangement • MET exon 14 mutation • RET mutation • ROS1 fusion • MET mutation • KRAS G12 • NTRK fusion
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    Xalkori (crizotinib) • Tagrisso (osimertinib) • Rozlytrek (entrectinib) • Lumakras (sotorasib)
    3d
    The first case of GOLGA5-RET fusion-positive malignant spindle cell sarcoma of the head and neck responsive to selpercatinib. (PubMed, Int Cancer Conf J)
    Following confirmation of multiple lung metastases, the patient was treated with doxorubicin monotherapy. Subsequent next-generation sequencing (NGS) revealed a RET fusion, leading to the diagnosis of an RET-rearranged spindle cell neoplasm. This case highlights the importance of genomic testing for certain spindle cell sarcomas and the potential benefit of RET-specific inhibitors against RET-altered sarcomas.
    Journal • IO biomarker
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    RET (Ret Proto-Oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CD34 (CD34 molecule) • SOX10 (SRY-Box 10) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6) • GOLGA5 (Golgin A5) • SYP (Synaptophysin)
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    RET fusion • RET rearrangement • RET positive
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    doxorubicin hydrochloride • Retevmo (selpercatinib)
    4d
    Selpercatinib for RET-positive advanced pancreatic cancer detected by liquid biopsy: a case-based insight. (PubMed, Pharmacogenomics)
    Emerging evidence from clinical trials supports the efficacy of RET inhibitors in RET-altered PDAC. Broader integration of genomic testing in PDAC may uncover new therapeutic opportunities and improve patient outcomes.
    Journal • Liquid biopsy
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    RET (Ret Proto-Oncogene)
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    RET fusion • RET positive
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    Retevmo (selpercatinib)
    5d
    Pan-cancer clinicopathological and genomic characteristics of peritoneal metastasis. (PubMed, NPJ Precis Oncol)
    Mutational signatures implicate ROS (SBS18), HR deficiency (SBS3), and SBS8 across ≥9 cancer types. These results establish foundational insights into PM biology, though future PM tissue profiling is warranted to overcome primary tumor bias in genomic data.
    Journal • Pan tumor
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    ER (Estrogen receptor) • RET (Ret Proto-Oncogene) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • TCF7L2 (Transcription Factor 7 Like 2) • TGFB1 (Transforming Growth Factor Beta 1)
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    RET mutation • ESR1 mutation
    7d
    An Interpretable Machine Learning Model for Predicting Occult Central Lymph Node Metastasis in Papillary Thyroid Cancer. (PubMed, J Clin Endocrinol Metab)
    This is the first study to identify RET fusion positivity as an independent OLNM risk factor in cN0 PTC. The developed RF model demonstrates moderate predictive performance for OLNM risk and provides a framework for integrating clinical, sonographic, and molecular data, and is deployed as a web calculator (https://predictingoccultlymphnodemetastasis.shinyapps.io/web3/).
    Journal
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    BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene)
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    BRAF mutation • RET fusion
    8d
    KRAS-Wild Pancreatic Cancer-More Targets than Treatment Possibilities? (PubMed, Cancers (Basel))
    Currently, selpercatinib, larotrectinib, and repotrectinib are approved by the FDA for the treatment of certain solid tumors harboring specific gene fusions. Recent studies on zenocutuzumab resulted in the FDA-accelerated approval for NGR1 fusion-positive NSCLC and PDAC. Germline mutations may specifically increase responsiveness to poly(ADP-ribose) polymerase (PARP) inhibitors or platinum-based treatments. Comprehensive genomic profiling, incorporating fusion detection and germline testing, is essential to identify patients who may benefit from precision-based approaches.
    Review • Journal • PARP Biomarker
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    KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR (Fibroblast Growth Factor Receptor) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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    KRAS mutation • KRAS wild-type • ALK fusion • RAS wild-type
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    Vitrakvi (larotrectinib) • Retevmo (selpercatinib) • Augtyro (repotrectinib) • Bizengri (zenocutuzumab-zbco)
    8d
    Accurate RET Fusion Detection in Solid Tumors Using RNA Sequencing Coverage Imbalance Analysis. (PubMed, Int J Mol Sci)
    Among the 18 RET fusion-positive samples, one was identified as an extremely rare case (RUFY3::RET), and two were determined to be novel fusions (FN1::RET, PPP1R21::RET). The findings of this study demonstrate that exon coverage imbalance analysis serves as a robust complement to computational RNA-seq analysis pipelines for the detection of clinically relevant RET fusions.
    Journal
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    RET (Ret Proto-Oncogene)
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    RET fusion • RET positive
    8d
    The shifting landscape of germline RET pathogenic variants with the introduction of panel testing. (PubMed, Surgery)
    RET pathogenic variants V804M, K666N, and C609Y were the most identified variants, particularly through broad panel testing, indicating increased incidental diagnosis of MEN2. The identification of previously unlisted variants underscores the need for dynamic guideline updates and ongoing curation to optimize clinical management of RET pathogenic variant carriers.
    Retrospective data • Journal
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    RET (Ret Proto-Oncogene)
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    RET C634* • RET V804* • RET positive
    12d
    Comparative genomic and clinicopathological analysis uncovers contrasting molecular profiles of canine and human thyroid carcinomas. (PubMed, Commun Biol)
    Thus, the genomic profile of canine FTC differs significantly from that of humans, with limited reliance on RAS/RAF signaling for oncogenic progression. Conversely, RET signaling likely underlies tumorigenesis in both canine and human MTC.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RET (Ret Proto-Oncogene)
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    KRAS mutation • BRAF mutation • NRAS mutation • HER-2 expression • RET mutation • HER-2 elevation
    14d
    Chylous Ascites, a Rare Adverse Reaction to Selpercatinib. (PubMed, Cureus)
    Reducing the selpercatinib dose and implementing a low long-chain triglyceride diet led to symptom relief, stable ascites, and maintained tumor response. This case highlights effective management of tyrosine kinase inhibitor (TKI)-induced CA without compromising cancer control.
    Journal
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    RET (Ret Proto-Oncogene)
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    RET fusion • RET positive
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    Retevmo (selpercatinib)
    22d
    Comprehensive Molecular Diagnostic Tests in Non-Small Cell Lung Cancer: Frequency of ALK, ROS1, RET, and Other Gene Fusions/Rearrangements in a Romanian Cohort. (PubMed, Cancers (Basel))
    These alterations were mutually exclusive with common drivers such as EGFR or KRAS. Detection of rare fusions highlights the therapeutic potential of comprehensive NGS profiling in Romanian NSCLC patients.
    Journal
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CD74 (CD74 Molecule) • TACC3 (Transforming acidic coiled-coil containing protein 3) • ETV6 (ETS Variant Transcription Factor 6) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
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    EGFR mutation • EGFR L858R • ALK positive • RET fusion • ALK fusion • ROS1 fusion
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    Oncomine Focus Assay