Ratti Margherita, Orlandi Elena, Hahne Jens Claus, Vecchia Stefano, Citterio Chiara, Anselmi Elisa, Toscani Ilaria, Ghidini Michele
Oncology and Hematology Department, Piacenza General Hospital, Via Taverna 49, 29121 Piacenza, Italy.
Centre for Evolution and Cancer, The Institute of Cancer Research, London SM2 5NG, UK.
Biomedicines. 2023 Sep 27;11(10):2650. 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.
在胃肠道（GI）癌发生过程中，成纤维细胞生长因子受体（FGFR）信号通路的失调起着关键作用。该通路的异常活性在约10%的胃癌中有所描述，而在肝内胆管癌（iCCA）中的频率增加，估计频率为10 - 16%。在过去几年中，已经开发出几种选择性FGFR抑制剂，并取得了有前景的结果。例如，靶向FGFR通路现在是治疗iCCA临床实践的基本组成部分，并且正在进行许多临床试验以测试抗FGFR药物在胃癌、结肠癌和胰腺癌中的安全性和有效性，结果各异。然而，抗FGFR药物的应答率适中且耐药性迅速出现，限制了它们的疗效并导致疾病进展。在这篇综述中，我们旨在探讨抗FGFR抑制剂在胃肠道癌方面的情况，特别关注选择性FGFR抑制剂以及可能导致克服耐药机制和药物诱导毒性的药物组合。
