Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15261, USA.
UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
Curr Oncol. 2024 Jul 29;31(8):4305-4317. doi: 10.3390/curroncol31080321.
Gastric cancer (GC) represents a major global health challenge as a highly prevalent disease 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 chemotherapy 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 Factor 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 targeting 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 outline 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.
胃癌（GC）是一个全球性的重大健康挑战，其发病率和死亡率均很高，预计在未来几年内还会进一步恶化。目前，我们对晚期胃癌的标准治疗方法是联合化疗和免疫疗法，其 1 年总生存率为 55%。为了寻找可靶向治疗的靶点，我们付出了巨大的努力，最终确定了成纤维细胞生长因子受体（FGFRs）家族，特别是 FGFR2 作为一个很有前途的靶点。FGFR2 在 GC 中过度表达，特别是弥漫型 GC，与预后不良有关。近年来，越来越多的针对 FGFR2 的小分子抑制剂和单克隆抗体进入临床试验。特别是针对 GC，这些药物目前正在不同阶段进行试验，作为单一疗法或与标准治疗联合应用，以期对 GC 的一个重要生物学轴产生有临床意义的影响。在这篇综述中，我们概述了 FGFR2 的基础生物学、它在 GC 中的潜在作用，以及目前正在临床试验中用于胃癌患者的各种 FGFR2 靶向药物，并推测了在临床上应用这些治疗方法的一些挑战。
