Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Nat Rev Urol. 2020 Nov;17(11):613-625. doi: 10.1038/s41585-020-00379-4. Epub 2020 Oct 12.
Gene fusions result from either structural chromosomal rearrangement or aberrations caused by splicing or transcriptional readthrough. The precise and distinctive presence of fusion genes in neoplastic tissues and their involvement in multiple pathways central to cancer development, growth and survival make them promising targets for personalized therapy. In genitourinary malignancies, rearrangements involving the E26 transformation-specific family of transcription factors have emerged as very frequent alterations in prostate cancer, especially the TMPRSS2-ERG fusion. In renal malignancies, Xp11 and t(6;11) translocations are hallmarks of a distinct pathological group of tumours described as microphthalmia-associated transcription factor family translocation-associated renal cell carcinomas. Novel druggable fusion events have been recognized in genitourinary malignancies, leading to the activation of several clinical trials. For instance, ALK-rearranged renal cell carcinomas have shown responses to alectinib and crizotinib. Erdafitinib has been tested for the treatment of FGFR-rearranged bladder cancer. Other anti-fibroblast growth factor receptor 3 (FGFR3) compounds are showing promising results in the treatment of bladder cancer, including infigratinib and pemigatinib, and all are currently in clinical trials.
基因融合是由于结构性染色体重排或剪接或转录通读引起的异常所致。融合基因在肿瘤组织中的精确和独特存在及其在癌症发展、生长和存活的多个中心途径中的参与，使它们成为个性化治疗的有前途的靶点。在泌尿生殖系统恶性肿瘤中，涉及 E26 转化特异性转录因子家族的重排已成为前列腺癌中非常常见的改变，特别是 TMPRSS2-ERG 融合。在肾恶性肿瘤中，Xp11 和 t(6;11)易位是描述为小眼相关转录因子家族易位相关肾细胞癌的独特病理组肿瘤的标志。在泌尿生殖系统恶性肿瘤中已经认识到新的可药物治疗的融合事件，导致了几项临床试验的开展。例如，ALK 重排的肾细胞癌对阿来替尼和克唑替尼有反应。厄达替尼已被测试用于治疗 FGFR 重排的膀胱癌。其他抗成纤维细胞生长因子受体 3（FGFR3）化合物在治疗膀胱癌方面显示出有希望的结果，包括英菲尼替尼和培米替尼，目前都在临床试验中。
