ArticleNPJ precision oncology2024
Adaptive Darwinian off-target resistance mechanisms to selective RET inhibition in RET driven cancer.
Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Combination of Selpercatinib and Trametinib Overcomes Resistance to RET Inhibitors in RET-Mutant Medullary Thyroid Carcinoma.JCO precision oncology · 2026Article
- Landscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Nanotechnology-Enabled Precision Therapy for Lung Cancer in Never-Smokers.Pharmaceutics · 2026Review
- Acquired TPM3::NTRK1 fusion as a novel off-target resistance mechanism to selpercatinib in RET-positive lung adenocarcinoma: a case report.Frontiers in oncology · 2026Article
- Identification of alkynyl nicotinamide HSN748 as a RET solvent-front mutant inhibitor with intracranial efficacy.RSC medicinal chemistry · 2025Article
- Consensus molecular subtyping of colorectal carcinoma brain metastases reveals a metabolic signature associated with poor patient survival.Molecular oncology · 2025Article
- Mechanisms of resistance to RET-directed therapies.Endocrine-related cancer · 2025Review
- Targeting Oncogenic RET Kinase by Simultaneously Inhibiting Kinase Activity and Degrading the Protein.Journal of medicinal chemistry · 2025Article
- Systemic therapies for medullary thyroid carcinoma: state of the art.Therapeutic advances in endocrinology and metabolism · 2025Review
- Multikinase and highly selective kinase inhibitors in the neoadjuvant treatment of patients with thyroid cancer.Exploration of targeted anti-tumor therapy · 2025Review
- DLK1 Is Associated with Stemness Phenotype in Medullary Thyroid Carcinoma Cell Lines.International journal of molecular sciences · 2024Article
- Tissue-Agnostic Targeting of Neurotrophic Tyrosine Receptor Kinase Fusions: Current Approvals and Future Directions.Cancers · 2024Review
- Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives.International journal of molecular sciences · 2024Review
- Targeting Oncogenic Gene Fusions in Lung Cancer.Cancer journal (Sudbury, Mass.)Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Patients treated with RET protein tyrosine kinase inhibitors (TKIs) selpercatinib or pralsetinib develop RET TKI resistance by secondary RET mutations or alterative oncogenes, of which alterative oncogenes pose a greater challenge for disease management because of multiple potential mechanisms and the unclear tolerability of drug combinations. A patient with metastatic medullary thyroid carcinoma (MTC) harboring a RET activation loop D898_E901del mutation was treated with selpercatinib. Molecular alterations were monitored with tissue biopsies and cfDNA during the treatment. The selpercatinib-responsive MTC progressed with an acquired ETV6::NTRK3 fusion, which was controlled by selpercatinib plus the NTRK inhibitor larotrectinib. Subsequently, tumor progressed with an acquired EML4::ALK fusion. Combination of selpercatinib with the dual NTRK/ALK inhibitor entrectinib reduced the tumor burden, which was followed by appearance of NTRK3 solvent-front G623R mutation. Preclinical experiments validated selpercatinib plus larotrectinib or entrectinib inhibited RET/NTRK3 dependent cells, whereas selpercatinib plus entrectinib was necessary to inhibit cells with RET/NTRK3/ALK triple alterations or a mixture of cell population carrying these genetic alterations. Thus, RET-altered MTC adapted to selpercatinib and larotrectinib with acquisition of ETV6::NTRK3 and EML4::ALK oncogenes can be managed by combination of selpercatinib and entrectinib providing proof-of-concept of urgency of incorporating molecular profiling in real-time and personalized N-of-1 care transcending one-size-fits-all approach.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.