ArticleInvestigational new drugs2020
Entrectinib resistance mechanisms in ROS1-rearranged non-small cell lung cancer.
Article in Investigational new drugs, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Serial Cell-Free DNA Sequencing inJCO precision oncology · 2024Trial
- An evaluation of taletrectinib for the treatment of ROS1+ non-small cell lung cancer.Expert review of anticancer therapy · 2026Review
- Bioinformatics And Experimental Insights Into Sotorasib Resistance Mechanisms in Non-small-cell Lung Cancer.Anti-cancer agents in medicinal chemistry · 2026Article
- High-throughput transcriptomic screening reveals entrectinib as a repositioning opportunity in 19q12 autism spectrum disorder.Scientific reports · 2025Article
- Identification of Key Genes and Signaling Pathways in Entrectinibresistant Non-small Cell Lung Cancer Using Bioinformatic Analysis and Experimental Verification.Current medicinal chemistry · 2025Article
- Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents.Cell communication and signaling : CCS · 2024Review
- CRISPR/Cas9-edited ROS1 + non-small cell lung cancer cell lines highlight differential drug sensitivity in 2D vs 3D cultures while reflecting established resistance profiles.Journal of translational medicine · 2024Article
- SOS2 modulates the threshold of EGFR signaling to regulate osimertinib efficacy and resistance in lung adenocarcinoma.Molecular oncology · 2024Article
- Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions.Biomedicines · 2024Review
- Transcriptomic analysis ofFrontiers in oncology · 2024Article
- 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
- Refractory response to entrectinib for ROS-1 rearranged NSCLC with concurrent de novo TP53 mutation showing good response to CNS lesion, but poor duration of response: A case report.Thoracic cancer · 2023Article
- SOS2 regulates the threshold of mutantbioRxiv : the preprint server for biology · 2023Article
- Efficacy of Crizotinib After Entrectinib Resistance Due toJTO clinical and research reports · 2023Article
- Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer.Molecular biomedicine · 2022Review
- MET gene amplification is a mechanism of resistance to entrectinib in ROS1+ NSCLC.Thoracic cancer · 2022Article
- Crizotinib Efficacy After Progression With Entrectinib in ROS1-Positive Lung Cancer: A Case Report.Cureus · 2022Article
- Clinical Value of NGS Genomic Studies for Clinical Management of Pediatric and Young Adult Bone Sarcomas.Cancers · 2021Article
- Paired analysis of tumor mutation burden calculated by targeted deep sequencing panel and whole exome sequencing in non-small cell lung cancer.BMB reports · 2021Article
- Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib inClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Entrectinib is a pan-tyrosine-kinase inhibitor that targets oncogenic rearrangements in NTRK, ROS1 and ALK. The combined results of two clinical trials demonstrated the efficacy of entrectinib in ROS1-rearranged NSCLC. Because the development of drug resistance is inevitable, it would be helpful to determine the mechanisms of entrectinib resistance in a ROS1-rearranged tumor model so that future therapeutic strategies can be developed. Here, we characterized the molecular basis of resistance in entrectinib-resistant ROS1-rearranged HCC78 cells (HCC78ER cells). These cells were analyzed by next-generation sequencing and genetic profiling, which revealed the acquisition of KRAS G12C and the amplification of KRAS and FGF3. However, there were no secondary mutations in the ROS1 kinase domain. We also found that sustained ERK activation was involved in entrectinib resistance, and that combined treatment with selumetinib resensitized HCC78ER cells to entrectinib in cell viability and colony formation assays. Our data suggest that activation of the RAS signaling pathway can cause entrectinib resistance in ROS1-rearranged NSCLC, and is unlikely to be overcome by sequential single agent ROS1-targeting strategies against such tumors. Instead, co-targeting ROS1 and MEK may be an effective strategy for overcoming entrectinib resistance in ROS1-rearranged NSCLC.
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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.