Glaser Alexander P, Fantini Damiano, Shilatifard Ali, Schaeffer Edward M, Meeks Joshua J
Northwestern University, Department of Urology, 303 E. Chicago Avenue, Tarry 16-703, Chicago, Illinois 60611, USA.
Nat Rev Urol. 2017 Feb 7;14(4):215-229. doi: 10.1038/nrurol.2017.11.
Survival of patients with urothelial carcinoma (including bladder cancer and upper tract urothelial carcinoma) is limited by our current approaches to staging, surgery, and chemotherapy. Large-scale, next-generation sequencing collaborations, such as The Cancer Genome Atlas, have already identified drivers and vulnerabilities of urothelial carcinoma. This disease has a high degree of mutational heterogeneity and a high frequency of somatic mutations compared with other solid tumours, potentially resulting in an increased neoantigen burden. Mutational heterogeneity is mediated by multiple factors including the apolipoprotein B mRNA editing enzyme catalytic polypeptide family of enzymes, smoking exposure, viral integrations, and intragene and intergene fusion proteins. The mutational landscape of urothelial carcinoma, including specific mutations in pathways and driver genes, such as FGFR3, ERBB2, PIK3CA, TP53, and STAG2, affects tumour aggressiveness and response to therapy. The next generation of therapies for urothelial carcinoma will be based on patient-specific targetable mutations found in individual tumours. This personalized-medicine approach to urothelial carcinoma has already resulted in unique clinical trial design and has the potential to improve patient outcomes and survival.
尿路上皮癌（包括膀胱癌和上尿路尿路上皮癌）患者的生存率受到我们目前分期、手术和化疗方法的限制。大规模的新一代测序合作项目，如癌症基因组图谱，已经确定了尿路上皮癌的驱动因素和易感性。与其他实体瘤相比，这种疾病具有高度的突变异质性和较高的体细胞突变频率，可能导致新抗原负担增加。突变异质性由多种因素介导，包括载脂蛋白B信使核糖核酸编辑酶催化多肽家族酶、吸烟暴露、病毒整合以及基因内和基因间融合蛋白。尿路上皮癌的突变图谱，包括途径和驱动基因中的特定突变，如FGFR3、ERBB2、PIK3CA、TP53和STAG2，会影响肿瘤的侵袭性和对治疗的反应。尿路上皮癌的下一代治疗将基于在个体肿瘤中发现的患者特异性可靶向突变。这种针对尿路上皮癌的个性化医疗方法已经导致了独特的临床试验设计，并有可能改善患者的治疗效果和生存率。
