ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2021
Structural basis of acquired resistance to selpercatinib and pralsetinib mediated by non-gatekeeper RET mutations.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses that pooled it.
What it found
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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
123 citing papers in PubMed, 2 syntheses or guidelines pooled it, 239 citations in OpenAlex.
- Selpercatinib versus multi-kinase inhibitors for advanced medullary thyroid cancer: A network meta-analysis of RET-targeted therapies.Frontiers in endocrinology · 2026Pooled it
- Design of new drugs for medullary thyroid carcinoma.Frontiers in oncology · 2022Pooled it
- Genomics and Multi-Omics to Guide Clinical Management in Thyroid Cancer.International journal of molecular sciences · 2026Review
- Targeted therapies in the management of advanced medullary thyroid cancer.The oncologist · 2026Review
- Development and Characterization of a Patient-DerivedJTO clinical and research reports · 2026Article
- Integrated multi-omics and single-cell analyses identify metabolic heterogeneity and therapeutic vulnerabilities in medullary thyroid cancer.British journal of cancer · 2026Article
- The combination of pralsetinib and bevacizumab enhances antitumor activity against KIF5B-RET lung cancer via PI3K/AKT pathway.Journal of thoracic disease · 2026Article
- Combination of Selpercatinib and Trametinib Overcomes Resistance to RET Inhibitors in RET-Mutant Medullary Thyroid Carcinoma.JCO precision oncology · 2026Article
- Targeting fusion proteins in solid tumors: from oncogenic mechanisms to clinical interventions.Acta pharmacologica Sinica · 2026Review
- In Silico Studies of Potent Tyrosine Kinase Inhibitors: Molecular Docking and Pharmacophore Modeling Approaches.Molecules (Basel, Switzerland) · 2026Article
- RET Signaling Pathway in Human Cancer: Oncogenic Mechanisms, Selective Inhibitors, and Emerging Resistance Strategies.International journal of molecular sciences · 2026Review
- 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
- Oligoprogression in NSCLC with Other Actionable Oncogenic Drivers Beyond EGFR and ALK: An Emerging Entity.International journal of molecular sciences · 2026Review
- Targeted therapy in thyroid cancer: molecular alterations and clinical management.Frontiers in endocrinology · 2026Review
- Response to Selpercatinib in aLung Cancer (Auckland, N.Z.) · 2026Article
- How to manage medullary thyroid carcinoma: current treatment strategies.Drugs in context · 2026Review
- Current State of the Neurotrophin-Based Pharmaceutics in the Treatment of Neurodegenerative Diseases and Neuroinflammation.Medical sciences (Basel, Switzerland) · 2025Review
- Review
- Redefining the Diagnostic and Therapeutic Landscape of Non-Small Cell Lung Cancer in the Era of Precision Medicine.Journal of clinical medicine · 2025Review
- Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSelpercatinib (LOXO-292) and pralsetinib (BLU-667) are highly potent RET-selective protein tyrosine kinase inhibitors (TKIs) for treating advanced RET-altered thyroid cancers and non-small-cell lung cancer (NSCLC). It is critical to analyze RET mutants resistant to these drugs and unravel the molecular basis to improve patient outcomes. PATIENTS AND
methodsCell-free DNAs (cfDNAs) were analyzed in a RET-mutant medullary thyroid cancer (MTC) patient and a CCDC6-RET fusion NSCLC patient who had dramatic response to selpercatinib and later developed resistance. Selpercatinib-resistant RET mutants were identified and cross-profiled with pralsetinib in cell cultures. Crystal structures of RET-selpercatinib and RET-pralsetinib complexes were determined based on high-resolution diffraction data collected with synchrotron radiation.
resultsRET
conclusionsRET mutations at the solvent front and the hinge are resistant to both drugs. Selpercatinib and pralsetinib use an unconventional mode to bind RET that avoids the interference from gatekeeper mutations but is vulnerable to non-gatekeeper mutations.
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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.