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Nagdas, S.; Saeed, A.; Saeed, A. Deciphering the FGFR2 Code: Innovative Targets in Gastric Cancer Therapy. Curr. Oncol. 2024, 31, 4305–4317. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/curroncol31080321](10.3390/curroncol31080321)  \nReceived: 19 June 2024  \nRevised: 26 July 2024  \nAccepted: 27 July 2024  \nPublished: 29 July 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland.  \nThis article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// [creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15261, USA; alirezatojjari@gmail.com  \n2 UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA; nagdass@upmc.edu  \n3 Department of Medicine, Ochsner Lafayette General Medical Center, Lafayette, LA 70503, USA; [asaeedmd@gmail.com](asaeedmd@gmail.com)  \n* Correspondence: [saeeda3@upmc.edu](saeeda3@upmc.edu); Tel.: +1‑412‑623‑2091  \nAbstract: Gastric cancer (GC) represents a major global health challenge as a highly prevalent dis‑ ease with high mortality whose global incidence and mortality are predicted to worsen over the coming years. To date, our standard of care for advanced gastric cancer of combination chemother‑ apy and immunotherapy has a 1‑year overall survival rate of 55% . Significant efforts have gone into identifying targetable alterations in gastric cancer, ultimately yielding the Fibroblast Growth Fac‑ tor Receptors (FGFRs) family, specifically FGFR2 as a promising target. FGFR2 is overexpressed in GC, particularly diffuse‑type GC, and is associated with poor prognostic outcomes. In recent years, there has been an increasing number of small molecule inhibitors and monoclonal antibodies target‑ ing FGFR2 that have entered into clinical trials. Specifically for GC, these agents are currently being trialed in various phases as monotherapies or with standard‑of‑care treatments to make a clinically meaningful impact on what appears to be an important biological axis of GC. In this review, we out‑ line the underlying biology of FGFR2, its putative role in GC, and the various FGFR2‑targeted agents currently in clinical trials for gastric cancer patients as well as postulate some challenges in adopting these therapeutics for clinically meaningful benefit.  \nKeywords: FGFR2; FGFR2‑targeted therapy; gastric cancer biomarkers; molecular oncology; precision medicine  \n1. Introduction  \nGastric cancer (GC) represents a major global health challenge, ranking as the fifth most prevalent cancer and the fourth leading cause of cancer‑related mortality worldwide. This malignancy not only impacts a significant number of individuals annually but also poses a growing public health concern due to increasing risk factors such as obesity and Helicobacter pylori infection, particularly in Asian countries. The projected rise in both incidence and mortality underscores the critical need for enhanced diagnostic and thera‑ peutic approaches [1] .  \nFor a long time, the backbone of therapy for advanced GC has been the use of fluo‑ ropyrimidine and platinum‑based chemotherapeutics. The advent of advanced molecular and genomic studies into GC has allowed for better characterization of this disease. The Cancer Genome Atlas (TCGA) genomic analysis identified four distinct subtypes in gas‑ tric cancer: tumors characterized by microsatellite instability (MSI), those positive for the Epstein–Barr virus (EBV), tumors with chromosomal instability (CIN), and those identified as genomically stable (GS) tumors [2] . Despite these approaches, the search for molecular markers","cbCaiq3nV9EnLiQg","https://ap.wps.com/l/cbCaiq3nV9EnLiQg","pdf",1112865,13,"English","# Abstract\n# Introduction\n## Current landscape of advanced gastric cancer therapy\n## Genomic subtypes and the need for actionable biomarkers\n## From earlier targeted approaches to HER2 success\n## FGFR/FGFR2 signaling rationale in gastric cancer","[{\"question\":\"Why is FGFR2 considered an important target in gastric cancer?\",\"answer\":\"FGFR2 is overexpressed in gastric cancer, particularly diffuse-type disease, and is associated with poor prognostic outcomes, making it a promising therapeutic target.\"},{\"question\":\"What are the current standard-of-care options for advanced gastric cancer discussed in the review?\",\"answer\":\"The review describes combination chemotherapy and immunotherapy as standard care for advanced gastric cancer, with a reported one-year overall survival rate of 55%.\"},{\"question\":\"How does the review connect FGFR2 signaling biology to cancer progression?\",\"answer\":\"It explains that FGFRs are receptor tyrosine kinases involved in signaling through fibroblast growth factors, regulating growth, survival, and differentiation; disruption, including FGFR2 gene amplification, links to tumorigenesis and progression.\"}]","Deciphering the FGFR2 Code: Innovative Targets in Gastric Cancer Therapy - Review | PDF",1789992150,33]