ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
MAPK Pathway Alterations Correlate with Poor Survival and Drive Resistance to Therapy in Patients with Lung Cancers Driven by
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- An evaluation of taletrectinib for the treatment of ROS1+ non-small cell lung cancer.Expert review of anticancer therapy · 2026Review
- Evolving Therapeutic Landscape of ROS1-Positive Non-Small Cell Lung Cancer: An Updated Review.Current oncology (Toronto, Ont.) · 2025Review
- Harnessing CRISPR/Cas9 to overcome targeted therapy resistance in non‑small cell lung cancer: Advances and challenges (Review).Oncology reports · 2025Review
- Visceral crisis in a patient with non-small cell lung cancer andTranslational lung cancer research · 2025Article
- Advances and future directions in ROS1 fusion-positive lung cancer.The oncologist · 2024Review
- Current treatment and novel insights regarding ROS1-targeted therapy in malignant tumors.Cancer medicine · 2024Review
- Differential network analysis of ROS1 inhibitors reveals lorlatinib polypharmacology through co-targeting PYK2.Cell chemical biology · 2024Article
- PAI-1 mediates acquired resistance to MET-targeted therapy in non-small cell lung cancer.PloS one · 2024Article
- Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.Frontiers in immunology · 2024Review
- Different effects of crizotinib treatment in two non-small cell lung cancer patients with SDC4::ROS1 fusion variants.Thoracic cancer · 2024Article
- From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC).Diagnostics (Basel, Switzerland) · 2023Review
- Combination Therapy With MDM2 and MEK Inhibitors Is Effective in Patient-Derived Models of Lung Adenocarcinoma With Concurrent Oncogenic Drivers and MDM2 Amplification.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Article
- Review
- Evolution of acquired resistance in a ROS1NPJ precision oncology · 2023Article
- Applications and advancements of CRISPR-Cas in the treatment of lung cancer.Frontiers in cell and developmental biology · 2023Review
- FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies.Frontiers in pharmacology · 2023Review
- ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer.International journal of cancer · 2022Article
- Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer.Molecular biomedicine · 2022Review
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- MYC Promotes Tyrosine Kinase Inhibitor Resistance in ROS1-Fusion-Positive Lung Cancer.Molecular cancer research : MCR · 2022Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeROS1 tyrosine kinase inhibitors (TKI) provide significant benefit in lung adenocarcinoma patients with ROS1 fusions. However, as observed with all targeted therapies, resistance arises. Detecting mechanisms of acquired resistance (AR) is crucial to finding novel therapies and improve patient outcomes. EXPERIMENTAL
designROS1 fusions were expressed in HBEC and NIH-3T3 cells either by cDNA overexpression (CD74/ROS1, SLC34A2/ROS1) or CRISPR-Cas9-mediated genomic engineering (EZR/ROS1). We reviewed targeted large-panel sequencing data (using the MSK-IMPACT assay) patients treated with ROS1 TKIs, and genetic alterations hypothesized to confer AR were modeled in these cell lines.
resultsEight of the 75 patients with a
conclusionsWe demonstrate that downstream activation of the MAPK pathway can mediate of innate acquired resistance to ROS1 TKIs and that patients harboring ROS1 fusion and concurrent downstream MAPK pathway alterations have worse survival. Our findings suggest a treatment strategy to target both aberrations.
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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.