ArticleTranslational lung cancer research2020
SRC and PIM1 as potential co-targets to overcome resistance in MET deregulated non-small cell lung cancer.
Article in Translational lung cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Exploring PIM1 Kinase as a Therapeutic Target: Mechanisms and Strategies in Cancer Treatment.International journal of molecular sciences · 2026Review
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- Review
- Unveiling Isorhapontigenin's therapeutic potential in lung cancer via integrated network pharmacology, molecular docking, and experimental validation.Scientific reports · 2025Article
- PIM1 kinase and its diverse substrate in solid tumors.Cell communication and signaling : CCS · 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
- Dual data and motif clustering improves the modeling and interpretation of phosphoproteomic data.Cell reports methods · 2022Article
- Genomic Characterization of Concurrent Alterations in Non-Small Cell Lung Cancer (NSCLC) Harboring Actionable Mutations.Cancers · 2021Article
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Authors and funding
19 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe role of MET alterations in non-small cell lung cancer (NSCLC) is increasing and several targeted agents are under evaluation. MET exon 14 skipping mutations and MET amplifications are associated with potential sensitivity to MET inhibition, though resistance mechanisms are emerging. In MET addicted cells, MET inhibition leads to activation of proviral integration site for Moloney murine leukemia virus-1 (PIM1). PIM1 and proto-oncogene tyrosine-protein kinase Src (SRC) can regulate the expression of receptor tyrosine kinases (RTKs), potentially inducing resistance to MET inhibition through cross-activation.
methodsWe evaluated the activity of class I-II MET inhibitors, the SRC inhibitor dasatinib, and pan-PIM inhibitors in four MET addicted cell lines. We assessed the effect of the dual MET/PIM and MET/SRC inhibition on cell viability and at the protein level. We evaluated RNA expression profiles of the cell lines. Advanced NSCLCs were also screened for MET alterations.
resultsAll cell lines were sensitive to class I-II MET inhibitors. All cell lines were resistant to single PIM and SRC inhibition. Dual MET/PIM inhibition was synergistic or additive in MET amplified cell lines and dual MET/SRC inhibition was highly synergistic in all MET addicted cell lines. The addition of an SRC inhibitor partially prevents the RTKs cross-activation. MET alterations were found in 9 out of 97 evaluable samples (9.3%); median overall survival in MET altered patients was 5 months (95% CI, 3 m-NA).
conclusionsWe identified a potential role of PIM inhibition in MET amplified tumors and of SRC inhibition in MET addicted tumors. Potential applications of this new treatment strategy warrant further evaluation.
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