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治疗胆管癌的FGFR小分子抑制剂研究进展
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Abstract:
由于基因扩增、激活突变和致癌融合，成纤维细胞生长因子(fibroblast growth factor, FGF)/FGFR系统的失调经常发生在肿瘤中。因此，FGF/FGFR靶向治疗的发展是一些基础、临床前和临床研究的重点。胆管癌(cholangiocarcinoma, CCA)是一种起源于胆管的肿瘤，化疗长期以来一直是转移性CCA的标准治疗方法，但最近的临床试验表明，成纤维细胞生长因子受体(fibroblast growth factor receptor, FGFR)抑制剂是一种有前景的治疗FGFR基因遗传改变的晚期CCA的新方法。本文综述了FGFR通路的生物学特性、CCA的遗传特征、CCA中重要的FGFR抑制剂临床试验，以及未来开发FGFR抑制剂用于CCA患者的有效临床应用的机遇和挑战。
Dysregulation of the fibroblast growth factor (FGF)/FGF receptor system often occurs in tumors due to gene amplification, activation mutations, and oncogenic fusions. Therefore, the development of FGF/FGFR-targeted therapies is the focus of some basic, preclinical and clinical studies. Cholangio-carcinoma is a tumor originating in the bile duct, and chemotherapy has long been the standard treatment for metastatic CCA, but recent clinical trials have shown that fibroblast growth factor re-ceptor inhibitors are a promising new treatment for advanced CCA with genetic alterations of the FGFR gene. This review reviews the biology of FGFR pathways, the genetic characteristics of CCA, the important clinical trials of FGFR inhibitors in CCA, and the opportunities and challenges for devel-oping effective clinical applications of FGFR inhibitors in CCA patients in the future.
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