ArticleFrontiers in oncology2019
SRC and MEK Co-inhibition Synergistically Enhances the Anti-tumor Effect in Both Non-small-cell Lung Cancer (NSCLC) and Erlotinib-Resistant NSCLC.
Article in Frontiers in oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Salvianolic Acid A Induces Ferroptosis in Non-Small Cell Lung Cancer via the SRC/YAP/GPX4 Axis.International journal of molecular sciences · 2026Article
- Bioinformatics-driven identification of pathogenic missense nsSNPs in the human proto-oncogene SRC and cancer susceptibility.Journal, genetic engineering & biotechnology · 2025Article
- Green SeaweedMarine drugs · 2024Article
- BCL2L11 Induction Mediates Sensitivity to Src and MEK1/2 Inhibition in Thyroid Cancer.Cancers · 2023Article
- Combining MEK and SRC inhibitors for treatment of colorectal cancer demonstrate increased efficacy in vitro but not in vivo.PloS one · 2023Article
- The Biology and Therapeutic Potential of the Src-YAP Axis in Non-Small Cell Lung Cancer (NSCLC).Cancers · 2022Article
- Multi-Omics Immune Interaction Networks in Lung Cancer Tumorigenesis, Proliferation, and Survival.International journal of molecular sciences · 2022Article
- Review
- The Pyrazolo[3,4-Biomedicines · 2022Article
- An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy.BMC cancer · 2022Article
- Pathway profiling of a novel SRC inhibitor, AZD0424, in combination with MEK inhibitors for cancer treatment.Molecular oncology · 2022Article
- Increased efficacy of gefitinib on cisplatin-resistant wild-type epidermal growth factor receptor non-small cell lung cancer cells.Translational cancer research · 2020Article
- The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC).Cancers · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-small-cell lung cancer (NSCLC) is the predominant form of lung cancer, and it is regulated by a complex signal transduction network. Single-agent targeted therapy often results in acquired resistance, which leads to treatment failure. In this study, we demonstrated that a combination of the kinase inhibitors trametinib and bosutinib can synergistically suppress the growth of NSCLC by inhibiting both the mitogen-activated protein kinase (MAPK) and proto-oncogene tyrosine-protein kinase (SRC) pathways. The combination was profiled against a panel of 22 NSCLC cell lines, including one erlotinib-resistant cell line, and this combination was found to show synergistic effects against 16 cell lines. NSCLC cell lines (HCC827, HCC827-erlotinib-resistant, and H1650) were treated with trametinib, bosutinib, or a combination of these drugs. The drug combination inhibited colony formation and induced cell apoptosis. A mechanism study showed that the phosphorylation of multiple kinases in the epidermal growth factor receptor (EGFR) signaling pathway in NSCLC was down-regulated. In addition, the combination significantly attenuated tumor growth of HCC827 xenografts with low toxicity. Our findings provide a theoretical basis for further study of the combination of MAPK and SRC pathway inhibitors in NSCLC, especially in the treatment of erlotinib-resistant NSCLC.
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