ArticleJournal of cancer research and clinical oncology2022
Cetuximab resistance induced by hepatocyte growth factor is overcome by MET inhibition in KRAS, NRAS, and BRAF wild-type colorectal cancers.
Article in Journal of cancer research and clinical oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Natural Monoterpene Stylosin Induced Anticancer Effects on Human Colon Carcinoma Cells.Pharmacology research & perspectives · 2026Article
- Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas.Cells · 2024Review
- Inhibition of autocrine HGF maturation overcomes cetuximab resistance in colorectal cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Exosomes derived from MDR cells induce cetuximab resistance in CRC via PI3K/AKT signaling‑mediated Sox2 and PD‑L1 expression.Experimental and therapeutic medicine · 2023Article
- Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling.Frontiers in pharmacology · 2023Review
- Article
- The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer.Diagnostics (Basel, Switzerland) · 2022Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
purposeRecent evidence has highlighted the role of hepatocyte growth factor (HGF) as a putative biomarker to predict EGFR inhibitor resistance. This study investigated the impact of plasma HGF levels on EGFR inhibition and the counter effect of MET inhibition in KRAS, NRAS, and BRAF (RAS/RAF) wild-type colorectal cancers (CRCs).
methodsPlasma HGF levels were analyzed with clinical outcomes of patients with metastatic CRC (mCRC) receiving palliative first-line chemotherapy. Then, in vitro experiments were conducted to validate the clinical findings and to establish pre-clinical evidence of MET inhibition by capmatinib.
resultsA total of 80 patients were included: cetuximab + FOLFIRI (n = 35) and bevacizumab + FOLFIRI (n = 45). Both progression-free survival (PFS) and overall survival (OS) were significantly lesser in the high vs low HGF group: median 11.8 vs. 24.7 months, respectively, for PFS (p = 0.009), and median 21.1 months vs. not reached, respectively, for OS (p = 0.018). The difference was significantly evident in the cetuximab group. In five RAS/RAF wild-type CRC cells, the addition of HGF activated ERK1/2 and AKT via MET phosphorylation, resulting in cetuximab resistance in vitro. In cetuximab-sensitive Caco-2 and SNU-C4 cells, capmatinib overcame cetuximab resistance in the presence of HGF by attenuating HGF-induced MET signaling activation.
conclusionPatients with mCRC receiving cetuximab + FOLFIRI who presented with high plasma HGF levels had significantly worse PFS and OS. Cetuximab resistance induced by HGF was mediated by AKT and ERK activation and overcome by MET inhibition in vitro.
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