ArticleCell reports2020
Inhibition of MEK1/2 Forestalls the Onset of Acquired Resistance to Entrectinib in Multiple Models of NTRK1-Driven Cancer.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Pooled it
- Development of PROTACs for targeted degradation of oncogenic TRK fusions.RSC chemical biology · 2026Article
- Review
- Development of PROTACs for targeted degradation of oncogenic TRK fusions.bioRxiv : the preprint server for biology · 2025Article
- Immune microenvironment and molecular mechanisms in endometrial cancer: implications for resistance and innovative treatments.Discover oncology · 2025Review
- NTRK1-fusion as an acquired resistance mechanism in EGFRex19 mutated NSCLC: a case report.Frontiers in pharmacology · 2025Article
- Multi-omics reveals lactylation-driven regulatory mechanisms promoting tumor progression in oral squamous cell carcinoma.Genome biology · 2024Article
- Targeting the peripheral neural-tumour microenvironment for cancer therapy.Nature reviews. Drug discovery · 2024Review
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- Preclinical Modeling of Pathway-Targeted Therapy of Human Lung Cancer in the Mouse.Cold Spring Harbor perspectives in medicine · 2024Review
- SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- SOS2 regulates the threshold of mutantbioRxiv : the preprint server for biology · 2023Article
- Bcl-xL Is a Key Mediator of Apoptosis Following KRASG12C Inhibition in KRASG12C-mutant Colorectal Cancer.Molecular cancer therapeutics · 2023Article
- Understanding the feasibility of chemotherapeutic and immunotherapeutic targets against non-small cell lung cancers: an update of resistant responses and recent combinatorial therapies.Exploration of targeted anti-tumor therapy · 2023Review
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- The Challenge and Opportunity of NTRK Inhibitors in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2022Review
- NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance.Frontiers in oncology · 2022Review
- Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of Resistance.Cancers · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
NTRK1 gene fusions are actionable drivers of numerous human malignancies. Here, we show that expression of the TPR-NTRK1 fusion kinase in immortalized mouse pancreatic ductal epithelial (IMPE) (pancreas) or mouse lung epithelial (MLE-12) cells is sufficient to promote rapidly growing tumors in mice. Both tumor models are exquisitely sensitive to targeted inhibition with entrectinib, a tropomyosin-related kinase A (TRKA) inhibitor. Initial regression of NTRK1-driven tumors is driven by induced expression of BIM, such that BIM silencing leads to a diminished response to entrectinib in vivo. However, the emergence of drug-resistant disease limits the long-term durability of responses. Based on the reactivation of RAF>MEK>ERK signaling observed in entrectinib-treated tumors, we show that the combination of entrectinib plus the MEK1/2 inhibitor cobimetinib dramatically forestalls the onset of drug resistance in vivo. Collectively, these data provide a mechanistic rationale for rapid clinical deployment of combined inhibition of TRKA plus MEK1/2 in NTRK1-driven cancers.
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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.