Targeting Fibroblast Growth Factor Receptor Pathway: Precision Medicine for Biliary Cancer and Beyond.

IF 4.3 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Seminars in liver disease Pub Date : 2023-05-01 DOI:10.1055/a-2049-3149
Pedro Luiz Serrano Uson Junior, Mitesh J Borad
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Abstract

Fibroblast growth factor receptor 2 (FGFR2) inhibitors are now being included in the treatment guidelines of multiple countries for patients with advanced cholangiocarcinoma (CCA). Activation of the FGF-FGFR pathway is related to proliferation and tumor progression. Targeting the FGF-FGFR pathway is effective and can yield durable responses in patients with CCA harboring FGFR2 fusions or rearrangements. In this review article, we address molecules and clinical trials evaluating FGFR inhibitors in advanced CCA. We will further discuss identified mechanisms of resistance and the strategies to overcome it. The incorporation of next-generation sequencing in advanced CCA and circulating tumor DNA on disease progression will unveil mechanisms of resistance and improve the development of future clinical trials and more selective drugs and combinations.

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靶向成纤维细胞生长因子受体途径:胆道癌及其他肿瘤的精准医学。
成纤维细胞生长因子受体2 (FGFR2)抑制剂现已被纳入多个国家晚期胆管癌(CCA)患者的治疗指南。FGF-FGFR通路的激活与增殖和肿瘤进展有关。靶向FGF-FGFR通路是有效的,并且可以在含有FGFR2融合或重排的CCA患者中产生持久的应答。在这篇综述文章中,我们讨论了FGFR抑制剂在晚期CCA中的分子和临床试验。我们将进一步讨论已确定的耐药性机制和克服耐药性的策略。将新一代测序纳入晚期CCA和循环肿瘤DNA的疾病进展将揭示耐药机制,并改善未来临床试验和更多选择性药物和组合的发展。
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来源期刊
Seminars in liver disease
Seminars in liver disease 医学-胃肠肝病学
CiteScore
8.20
自引率
2.40%
发文量
38
期刊介绍: Seminars in Liver Disease is a quarterly review journal that publishes issues related to the specialties of hepatology and gastroenterology. As the premiere review journal in the field, Seminars in Liver Disease provides in-depth coverage with articles and issues focusing on topics such as cirrhosis, transplantation, vascular and coagulation disorders, cytokines, hepatitis B & C, Nonalcoholic Steatosis Syndromes (NASH), pediatric liver diseases, hepatic stem cells, porphyrias as well as a myriad of other diseases related to the liver. Attention is also given to the latest developments in drug therapy along with treatment and current management techniques. Seminars in Liver Disease publishes commissioned reviews. Unsolicited reviews of an exceptional nature or original articles presenting remarkable results will be considered, but case reports will not be published.
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