Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana, USA
J Clin Pathol. 2021 Aug;74(8):491-495. doi: 10.1136/jclinpath-2020-207115. Epub 2021 Mar 17.
Dysregulation of fibroblast growth factor receptors () has been implicated in several human malignancies, including urothelial carcinoma. In urothelial carcinoma, the oncogenic role of mutated is mediated by the RAS-mitogen-activated protein kinase pathway, resembling the effects observed with activated Activating somatic mutations of are clustered in three hotspots in exons 7, 10 and 15, and are almost always missense mutations leading to amino acid substitution in the external, transmembrane or intracellular regions of the receptor. A fusion of to transforming acid coiled-coil containing protein 3, amplification and alternative splicing leading to aberrant activation are less common molecular alterations. In April 2020, the Food and Drug Administration (FDA) approved the first targeted therapy, erdafitinib, in patients with locally advanced or metastatic bladder cancer who have progressed on platinum-based chemotherapy. Herein, we reviewed the normal structure and function of We also explored its role in the development of urothelial carcinoma and major developments in the -targeted therapy.
成纤维细胞生长因子受体()失调与几种人类恶性肿瘤有关,包括膀胱癌。在膀胱癌中,突变的致癌作用是通过 RAS-有丝分裂原激活蛋白激酶途径介导的,类似于观察到的激活的作用。 的体细胞激活突变集中在 7、10 和 15 号外显子的三个热点中,几乎总是导致受体外部、跨膜或细胞内区域的氨基酸取代的错义突变。 与转化酸性卷曲螺旋蛋白 3 的融合、扩增和导致异常 激活的选择性剪接是不太常见的分子改变。2020 年 4 月,美国食品和药物管理局(FDA)批准了第一种针对 的靶向治疗药物厄达替尼,用于接受铂类化疗进展的局部晚期或转移性膀胱癌患者。在此,我们复习了 的正常结构和功能。我们还探讨了它在膀胱癌发展中的作用以及 - 靶向治疗的主要进展。