ArticleNature communications2022
The evolution of RET inhibitor resistance in RET-driven lung and thyroid cancers.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 65 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 3 syntheses or guidelines pooled it, 105 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
- 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2025Guideline
- Design of new drugs for medullary thyroid carcinoma.Frontiers in oncology · 2022Pooled it
- Safety, pharmacokinetics and efficacy of HA121-28 in patients with advanced solid tumors and RET fusion-positive non-small-cell lung cancer: a multicenter, open-label, single-arm phase 1/2 trial.Signal transduction and targeted therapy · 2025Trial
- Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial.The Lancet. Oncology · 2022Trial
- Evolving precision: Updates in targeted therapy for cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2026Review
- Inhibition of SHP2 enhances the effects of selective receptor tyrosine kinase inhibitors in untreated preclinical models of RET-mutated thyroid cancer.Investigational new drugs · 2026Article
- Clinical Activity of RET TKI Plus Chemotherapy After Progression on a RET TKI in aJTO clinical and research reports · 2026Article
- Modeling acquired TKI resistance and effective combination therapeutic strategies in murine RET+ lung adenocarcinoma.Cancer letters · 2026Article
- Combination of Selpercatinib and Trametinib Overcomes Resistance to RET Inhibitors in RET-Mutant Medullary Thyroid Carcinoma.JCO precision oncology · 2026Article
- Machine learning-enhanced QSAR modeling for predicting drug efficacy against the RET V804M kinase domain mutation.Molecular diversity · 2026Article
- Dual targeting of RET and SRC synergizes in RET fusion-positive cancer cells.Molecular oncology · 2026Article
- RET Signaling Pathway in Human Cancer: Oncogenic Mechanisms, Selective Inhibitors, and Emerging Resistance Strategies.International journal of molecular sciences · 2026Review
- Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Review
- Epigenetic dysregulation and therapeutic targeting of RET receptor tyrosine kinase in high-risk KMT2A-rearranged acute myeloid leukaemia.British journal of haematology · 2025Article
- Hinge binder modification into imidazopyridine for targeting actionable mutations of RET kinase.RSC medicinal chemistry · 2025Article
- Review
- MET and NF2 alterations confer primary and early resistance to first-line alectinib treatment in ALK-positive non-small-cell lung cancer.Molecular oncology · 2025Article
- Identification of alkynyl nicotinamide HSN748 as a RET solvent-front mutant inhibitor with intracranial efficacy.RSC medicinal chemistry · 2025Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
32 authors at 2 institutions in 1 country.
Funding
Abstract
The efficacy of the highly selective RET inhibitor selpercatinib is now established in RET-driven cancers, and we sought to characterize the molecular determinants of response and resistance. We find that the pre-treatment genomic landscape does not shape the variability of treatment response except for rare instances of RAS-mediated primary resistance. By contrast, acquired selpercatinib resistance is driven by MAPK pathway reactivation by one of two distinct routes. In some patients, on- and off-target pathway reactivation via secondary RET solvent front mutations or MET amplifications are evident. In other patients, rare RET-wildtype tumor cell populations driven by an alternative mitogenic driver are selected for by treatment. Multiple distinct mechanisms are often observed in the same patient, suggesting polyclonal resistance may be common. Consequently, sequential RET-directed therapy may require combination treatment with inhibitors targeting alternative MAPK effectors, emphasizing the need for prospective characterization of selpercatinib-treated tumors at the time of monotherapy progression.
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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.