ArticleOncogene2015
Synthetic lethal screening reveals FGFR as one of the combinatorial targets to overcome resistance to Met-targeted therapy.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies.Cancers · 2025Review
- Targeting ITGβ3 to Overcome Trastuzumab Resistance through Epithelial-Mesenchymal Transition Regulation in HER2-Positive Breast Cancer.International journal of molecular sciences · 2024Article
- Overcoming Vemurafenib Resistance in Metastatic Melanoma: Targeting Integrins to Improve Treatment Efficacy.International journal of molecular sciences · 2024Article
- Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation.Cancers · 2024Review
- Review
- An In Vitro Analysis of TKI-Based Sequence Therapy in Renal Cell Carcinoma Cell Lines.International journal of molecular sciences · 2023Article
- Targeting MET and FGFR in Relapsed or Refractory Acute Myeloid Leukemia: Preclinical and Clinical Findings, and Signal Transduction Correlates.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth.International journal of biological sciences · 2023Article
- DW14383 is an irreversible pan-FGFR inhibitor that suppresses FGFR-dependent tumor growth in vitro and in vivo.Acta pharmacologica Sinica · 2021Article
- Therapeutic implications of fibroblast growth factor receptor inhibitors in a combination regimen for solid tumors.Oncology letters · 2020Review
- Aggressive pulmonary adenocarcinoma with new FGFR translocation and cMET mutation not responsive to crizotinib and nintedanib treatment: a case report.Translational cancer research · 2020Article
- Article
- LncRNAs GIHCG and SPINT1-AS1 Are Crucial Factors for Pan-Cancer Cells Sensitivity to Lapatinib.Frontiers in genetics · 2019Article
- TNFAIP3 is required for FGFR1 activation-promoted proliferation and tumorigenesis of premalignant DCIS.COM human mammary epithelial cells.Breast cancer research : BCR · 2018Article
- Deep analysis of acquired resistance to FGFR1 inhibitor identifies MET and AKT activation and an expansion ofOncotarget · 2018Article
- SOMCL-085, a novel multi-targeted FGFR inhibitor, displays potent anticancer activity in FGFR-addicted human cancer models.Acta pharmacologica Sinica · 2018Article
- Article
- Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival.Oncotarget · 2016Article
- Novel strategy for a bispecific antibody: induction of dual target internalization and degradation.Oncogene · 2016Article
- Activation of the Met kinase confers acquired drug resistance in FGFR-targeted lung cancer therapy.Oncogenesis · 2016Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Met is a receptor tyrosine kinase that promotes cancer progression. In addition, Met has been implicated in resistance of tumors to various targeted therapies such as epidermal growth factor receptor inhibitors in lung cancers, and has been prioritized as a key molecular target for cancer therapy. However, the underlying mechanism of resistance to Met-targeting drugs is poorly understood. Here, we describe screening of 1310 genes to search for key regulators related to drug resistance to an anti-Met therapeutic antibody (SAIT301) by using a small interfering RNA-based synthetic lethal screening method. We found that knockdown of 69 genes in Met-amplified MKN45 cells sensitized the antitumor activity of SAIT301. Pathway analysis of these 69 genes implicated fibroblast growth factor receptor (FGFR) as a key regulator for antiproliferative effects of Met-targeting drugs. Inhibition of FGFR3 increased target cell apoptosis through the suppression of Bcl-xL expression, followed by reduced cancer cell growth in the presence of Met-targeting drugs. Treatment of cells with the FGFR inhibitors substantially restored the efficacy of SAIT301 in SAIT301-resistant cells and enhanced the efficacy in SAIT301-sensitive cells. In addition to FGFR3, integrin β3 is another potential target for combination treatment with SAIT301. Suppression of integrin β3 decreased AKT phosphorylation in SAIT301-resistant cells and restored SAIT301 responsiveness in HCC1954 cells, which are resistant to SAIT301. Gene expression analysis using CCLE database shows that cancer cells with high levels of FGFR and integrin β3 are resistant to crizotinib treatment, suggesting that FGFR and integrin β3 could be used as predictive markers for Met-targeted therapy and provide a potential therapeutic option to overcome acquired and innate resistance for the Met-targeting drugs.
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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.