Targeting FGFR Pathways in Gastrointestinal Cancers: New Frontiers of Treatment

• Published in: Biomedicines Vol. 11; no. 10; p. 2650
• Main Authors: Ratti, Margherita, Orlandi, Elena, Hahne, Jens Claus, Vecchia, Stefano, Citterio, Chiara, Anselmi, Elisa, Toscani, Ilaria, Ghidini, Michele
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 27-09-2023; MDPI
• Subjects: Angiogenesis; Cancer therapies; Carcinogenesis; Chemotherapy; Cholangiocarcinoma; Clinical trials; Colon cancer; Colorectal cancer; Development and progression; Drug therapy, Combination; FDA approval; FGFR pathways; Fibroblast growth factor receptors; Fibroblast growth factors; Fibroblasts; gastrointestinal cancers; Gene amplification; Homeostasis; Kinases; Ligands; Medical prognosis; Metastasis; Monoclonal antibodies; Mutation; Pancreatic cancer; Proteins; Review; Signal transduction; Stomach cancer; target therapies; Toxicity; Tumors
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11102650

In carcinogenesis of the gastrointestinal (GI) tract, the deregulation of fibroblast growth factor receptor (FGFR) signaling plays a critical role. The aberrant activity of this pathway is described in approximately 10% of gastric cancers and its frequency increases in intrahepatic cholangiocarcinomas (iCCAs), with an estimated frequency of 10–16%. Several selective FGFR inhibitors have been developed in the last few years with promising results. For example, targeting the FGFR pathway is now a fundamental part of clinical practice when treating iCCA and many clinical trials are ongoing to test the safety and efficacy of anti-FGFR agents in gastric, colon and pancreatic cancer, with variable results. However, the response rates of anti-FGFR drugs are modest and resistances emerge rapidly, limiting their efficacy and causing disease progression. In this review, we aim to explore the landscape of anti-FGFR inhibitors in relation to GI cancer, with particular focus on selective FGFR inhibitors and drug combinations that may lead to overcoming resistance mechanisms and drug-induced toxicities.