ArticleBritish journal of cancer2016
Efficacy of focal adhesion kinase inhibition in non-small cell lung cancer with oncogenically activated MAPK pathways.
Article in British journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Focal Adhesion and Cancer Cell Cycle-Associated Resistance.ACS omega · 2026Review
- In vitro synergistic effect of AXL, FAK and ErbB receptors inhibitors for head and neck cancer.Biology direct · 2025Article
- Focal adhesion kinase (FAK): emerging target for drug-resistant malignant tumors.Molecular biology reports · 2025Review
- FAK inhibition disrupts tumor growth, apoptosis, and transcriptional regulation in GI-NETs.Endocrine oncology (Bristol, England) · 2025Article
- Design and investigation of interactions of novel peptide conjugates of purine and pyrimidine derivatives with EGFR and its mutant T790M/L858R: an in silico and laboratory study.Molecular diversity · 2024Article
- DRD1 suppresses cell proliferation and reduces EGFR activation and PD-L1 expression in NSCLC.Molecular oncology · 2024Article
- Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy.Journal of translational medicine · 2024Review
- Focal adhesion kinase: from biological functions to therapeutic strategies.Experimental hematology & oncology · 2023Review
- DUSP5P1 promotes gastric cancer metastasis and platinum drug resistance.Oncogenesis · 2022Article
- Focal adhesion kinase inhibitors prevent osteoblast mineralization in part due to suppression of Akt-mediated stabilization of osterix.Journal of bone oncology · 2022Article
- Identification of genes and pathways leading to poor prognosis of non-small cell lung cancer using integrated bioinformatics analysis.Translational cancer research · 2022Article
- FAK in Cancer: From Mechanisms to Therapeutic Strategies.International journal of molecular sciences · 2022Review
- Targeting the FAK-Src Complex in Desmoplastic Small Round Cell Tumors, Ewing Sarcoma, and Rhabdomyosarcoma.Sarcoma · 2022Article
- Bioinformatics and System Biology Approach to Reveal the Interaction Network and the Therapeutic Implications for Non-Small Cell Lung Cancer Patients With COVID-19.Frontiers in pharmacology · 2022Article
- Novel Antibody Exerts Antitumor Effect through Downregulation of CD147 and Activation of Multiple Stress Signals.Journal of oncology · 2022Article
- Crosstalk between protein kinases AKT and ERK1/2 in human lung tumor-derived cell models.Frontiers in oncology · 2022Article
- Focal adhesion kinase inhibitors, a heavy punch to cancer.Discover oncology · 2021Review
- Uncovering the Anti-Lung-Cancer Mechanisms of the Herbal Drug FDY2004 by Network Pharmacology.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Focal adhesion kinase confers pro-migratory and antiapoptotic properties and is a potential therapeutic target in Ewing sarcoma.Molecular oncology · 2020Article
- Crosstalk between let-7a-5p and BCL-xL in the Initiation of Toxic Autophagy in Lung Cancer.Molecular therapy oncolytics · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundFocal adhesion kinase (FAK) is overexpressed in many types of tumours, including lung cancer. Y15, a small molecule which inhibits Y397 FAK autophosphorylation, decreases growth of human neuroblastoma, breast and pancreatic cancers. In this study, we investigated the in vitro and in vivo effects of Y15, and the underlying mechanism on non-small cell lung cancer cells.
methodsThe cytotoxic effects of Y15 targeting FAK signalling were evaluated. Gene-knockdown experiments were performed to determine the anti-cancer mechanism. Xenografts with RAS or EGFR mutations were selected for in vivo Y15 treatment.
resultsY15 blocked autophosphorylation of FAK in a time- and dose-dependent manner. It caused dose-dependent decrease of lung cancer cell viability and clonogenicity. Y15 inhibited tumour growth of RAS-mutant (A549 with KRAS mutation and H1299 with NRAS mutation), as well as epidermal growth factor receptor (EGFR) mutant (H1650 and H1975) lung cancer xenografts. JNK activation is a mechanism underlying Y15-induced Bcl-2 and Mcl-1 downregulation. Moreover, knockdown of Bcl-2 or Bcl-xL potentiated the effects of Y15. The combination of various inhibitors of the Bcl-2 family of proteins with FAK inhibitors demonstrated synergy in multiple lung cancer cell lines in vitro.
conclusionsFAK inhibition demonstrated efficacy both in vitro and in vivo in lung cancers with either oncogenic RAS or EGFR mutations. In addition, FAK inhibition in combination with inhibitors of Bcl-2 family of anti-apoptotic proteins has synergistic activity in these MAPK-activated non-small cell lung cancer cell line models.
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