ArticleProceedings of the National Academy of Sciences of the United States of America2013
Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 117 citations in OpenAlex.
- Met Receptor Tyrosine Kinase and Chemoprevention of Oral Cancer.Journal of the National Cancer Institute · 2018Trial
- A TMED3-governed disulfidptosis-related diagnostic signature reveals tumor microenvironment remodeling in intrahepatic cholangiocarcinoma.Frontiers in immunology · 2026Article
- Zidesamtinib Selective Targeting of Diverse ROS1 Drug-Resistant Mutations.Molecular cancer therapeutics · 2025Article
- Article
- Targeting ROS1 rearrangements in non-small cell lung cancer: Current insights and future directions.Cancer · 2025Review
- Current treatment and novel insights regarding ROS1-targeted therapy in malignant tumors.Cancer medicine · 2024Review
- 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
- Discovery of oncogenic ROS1 missense mutations with sensitivity to tyrosine kinase inhibitors.EMBO molecular medicine · 2023Article
- Therapeutical Options in ROS1-Rearranged Advanced Non Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- MYC Promotes Tyrosine Kinase Inhibitor Resistance in ROS1-Fusion-Positive Lung Cancer.Molecular cancer research : MCR · 2022Article
- Utility of the Ba/F3 cell system for exploring on-target mechanisms of resistance to targeted therapies for lung cancer.Cancer science · 2022Review
- Resistance Profile and Structural Modeling of Next-Generation ROS1 Tyrosine Kinase Inhibitors.Molecular cancer therapeutics · 2022Article
- Foretinib induces G2/M cell cycle arrest, apoptosis, and invasion in human glioblastoma cells through c-MET inhibition.Cancer chemotherapy and pharmacology · 2021Article
- Pharmacophore-based designing of putative ROS-1 targeting agents for NSCLC.Molecular diversity · 2021Article
- Identification of Flavonoids as Putative ROS-1 Kinase Inhibitors Using Pharmacophore Modeling for NSCLC Therapeutics.Molecules (Basel, Switzerland) · 2021Article
- ROS1-dependent cancers - biology, diagnostics and therapeutics.Nature reviews. Clinical oncology · 2021Review
- NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors.Communications biology · 2020Article
- Review
- Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion.Therapeutic advances in medical oncology · 2020Review
- Divergent Polypharmacology-Driven Cellular Activity of Structurally Similar Multi-Kinase Inhibitors through Cumulative Effects on Individual Targets.Cell chemical biology · 2019Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The rapidly growing recognition of the role of oncogenic ROS1 fusion proteins in the malignant transformation of multiple cancers, including lung adenocarcinoma, cholangiocarcinoma, and glioblastoma, is driving efforts to develop effective ROS1 inhibitors for use as molecularly targeted therapy. Using a multidisciplinary approach involving small molecule screening in combination with in vitro and in vivo tumor models, we show that foretinib (GSK1363089) is a more potent ROS1 inhibitor than crizotinib (PF-02341066), an ALK/ROS inhibitor currently in clinical evaluation for lung cancer patients harboring ROS1 rearrangements. Whereas crizotinib has demonstrated promising early results in patients with ROS1-rearranged non-small-cell lung carcinoma, recently emerging clinical evidence suggests that patients may develop crizotinib resistance due to acquired point mutations in the kinase domain of ROS1, thus necessitating identification of additional potent ROS1 inhibitors for therapeutic intervention. We confirm that the ROS1(G2032R) mutant, recently reported in clinical resistance to crizotinib, retains foretinib sensitivity at concentrations below safe, clinically achievable levels. Furthermore, we use an accelerated mutagenesis screen to preemptively identify mutations in the ROS1 kinase domain that confer resistance to crizotinib and demonstrate that these mutants also remain foretinib sensitive. Taken together, our data strongly suggest that foretinib is a highly effective ROS1 inhibitor, and further clinical investigation to evaluate its potential therapeutic benefit for patients with ROS1-driven malignancies is warranted.
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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.