PO.CL07.02 · 临床研究
FGFR2可能是某些类型癌症的一个有前景的治疗靶点：1312例FGFR2异常肿瘤的分析
FGFR2 might be a promising therapeutic target for some types of carcinomas: Analysis of 1312 tumors with FGFR2 abnormalities
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：成纤维细胞生长因子受体2（FGFR2）基因的遗传异常，包括扩增、融合和突变，已在多种实体瘤中被报道。虽然针对FGFR2融合的分子靶向治疗已被证明在胆管癌中有效，但FGFR2抑制剂在其他各类实体瘤中的治疗意义仍不明确。日本的癌症基因组学与先进治疗中心（C-CAT）数据库整合了实体瘤癌症基因panel检测病例的基因组和临床信息。本研究旨在利用C-CAT数据库阐明FGFR2异常的临床病理学意义。
材料与方法：2019年6月至2025年6月期间，共有101,231例实体瘤患者被登记进C-CAT数据库。在这101,231例中，对1312例具有FGFR2基因异常的病例进行了分析。评估了肿瘤类型分布、共突变以及对FGFR抑制剂的反应。在接受FGFR靶向治疗的患者中评估了疾病控制率（DCR）。
结果：FGFR2改变包括515例扩增、280例融合和568例突变。这些异常最常见于胆道（271例）、食管/胃（231例）和乳腺（211例）。扩增在食管/胃（205例）和乳腺（105例）中较为常见。FGFR2融合最常见于胆道（163例），其次为乳腺（21例）、胰腺（13例）。突变常见于子宫（111例）、乳腺（89例）和胆道（86例）。在1312例FGFR2改变病例中，有85例接受了FGFR2抑制剂治疗。在这85例中，49例实现了DCR，其中44例为胆道癌。
结论：FGFR2可能不仅是伴融合的胆管癌的一个有前景的治疗靶点，也是伴FGFR2改变的食管/胃癌和乳腺癌的有前景的治疗靶点。
查看英文原文 English abstract
Background: Genetic abnormalities of the fibroblast growth factor receptor 2 ( FGFR2 ) gene, including amplification, fusions, and mutations, have been reported in various solid tumors. While molecular targeted therapies against FGFR2 fusion have been proved to be useful in cholangiocarcinoma, the therapeutic significance of FGFR2 inhibitors remains unclear in other various solid cancers. Genomic and clinical information from solid tumor cancer gene panel testing cases is consolidated in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. This study aimed to utilize the C-CAT database to clarify the clinical-pathological significance of FGFR2 abnormalities.
Materials & Methods: A total of 101,231 patients with solid cancer have been registered in the C-CAT database between June 2019 and June 2025. Of the 101,231 cases, 1312 cases with FGFR2 gene abnormalities were analyzed. Tumor type distribution, co-mutations, and responses to FGFR inhibitors were evaluated. Disease control rate (DCR) was assessed in patients who received FGFR-targeted therapy.
Result: FGFR2 alterations included amplification in 515 cases, fusion in 280 cases, and mutations in 568 cases. Their abnormalities were detected most frequently in the biliary tract (271 cases), esophagus/stomach (231 cases), and breast (211 cases). Amplification was frequent in the esophagus/stomach (205 cases) and breast (105 cases). FGFR2 fusions are frequently detected in the biliary tract (163 cases), followed by breast (21 cases), pancreas (13 cases). Mutations were frequent in the uterus (111 cases), breast (89 cases), and biliary tract (86 cases). Among 1312 FGFR2 alteration cases, FGFR2 inhibitors were administered in 85 cases. Of the 85 cases, DCR was achieved in 49 cases, 44 cases of which were biliary tract cancer.
Conclusions: FGFR2 might be a promising therapeutic target not only for cholangiocarcinoma with fusion but also for esophagus/stomach cancer and breast cancer with FGFR2 alterations.
利益披露 Disclosure
H. Nishikubo, None.