靶向成纤维生长因子受体治疗胆管细胞癌的临床研究现状

Clinical research status of targeted fibroblast growth factor receptor in the treatment of cholangiocarcinoma

胆管细胞癌(CCA)是起源于胆管上皮细胞的恶性肿瘤,其手术根治性切除率低,术后易复发转移,疗效极差。对于晚期或不可切除的患者,局部和全身化疗是主要的治疗选择,但是疗效欠佳。由于手术治疗及化疗等疗效有限,靶向治疗逐渐成为胆管癌研究热点。近年来,随着对CCA分子病理机制认识的深入,肿瘤生物靶向治疗发展迅速,临床应用潜力巨大。胆管癌中成纤维细胞生长因子受体(FGFR)突变频率较高,FGFR基因融合、激活突变及扩增与胆管癌发生发展密切相关。目前,多种FGFR抑制药已应用于胆管癌临床试验,并取得初步成效。本文以胆管癌临床前研究结果为基础,结合国内外开展的FGFR抑制药临床试验,对胆管癌FGFR靶向治疗在临床试验中的研究现状进行综述,为进一步深入研究提供参考。

Cholangiocarcinoma(CCA) is a malignant tumor originating from bile duct epithelial cells. Its radical resection rate is low, and it is prone to recurrence and metastasis after surgery, and the curative effect is extremely poor. For advanced or unresectable patients, local and systemic chemotherapy are the main treatment options, but the efficacy is suboptimal. Due to the limited efficacy of surgery and chemotherapy, targeted therapy has gradually become a research hotspot in cholangiocarcinoma. In recent years, with the deepening of the understanding of the molecular pathological mechanism of CCA, tumor biological targeted therapy has developed rapidly and has great potential for clinical application. The mutation frequency of fibroblast growth factor receptor(FGFR) in cholangiocarcinoma is high, and FGFR gene fusion, activating mutation and amplification are closely related to the occurrence and development of cholangiocarcinoma;a variety of FGFR inhibitors have been used in clinical trials of cholangiocarcinoma, and Preliminary results have been achieved. Based on the results of preclinical research on cholangiocarcinoma, combined with the clinical trials of FGFR inhibitor drugs carried out at home and abroad, this paper reviews the research status of FGFR-targeted therapy for cholangiocarcinoma in clinical trials, and provides references for further in-depth research.