Balar Arjun V, Milowsky Matthew I
Memorial Sloan-Kettering Cancer Center, New York, New York.
Clin Adv Hematol Oncol. 2012 Aug;10(8):504-16.
Invasive urothelial cancer is an aggressive, biologically heterogeneous disease. Most patients present with non-muscle invasive bladder cancer involving the epithelium as exophytic tumors, in situ carcinoma, or minimally invasive disease involving the lamina propria. Such patients are typically managed with complete transurethral resection with or without intravesical therapy. Muscle invasive urothelial cancer, however, is biologically and clinically distinct. This subtype is characterized by mutations or deletions in tumor suppressor genes, such as TP53, Rb, and PTEN, leading to genomic instability and a more aggressive phenotype. Survival in advanced disease is poor with currently available treatment strategies. Technological advances in the ability to molecularly characterize human cancer have led to the identification of genetic alterations that may be therapeutically exploitable. Novel chemotherapies, such as antifolates and taxanes, have shown promise in urothelial cancer. Agents against novel molecular targets, such as the human epidermal receptor (HER) and vascular endothelial growth factor receptor (VEGFR), are being investigated. This review article focuses on the current status of novel chemotherapeutic and targeted agents as well as immunotherapy currently in clinical development in invasive urothelial cancer.
浸润性尿路上皮癌是一种侵袭性、生物学异质性疾病。大多数患者表现为非肌层浸润性膀胱癌，包括外生性肿瘤累及上皮、原位癌或累及固有层的微浸润性疾病。此类患者通常采用经尿道完全切除术治疗，可联合或不联合膀胱内治疗。然而，肌层浸润性尿路上皮癌在生物学和临床方面都有所不同。这种亚型的特征是肿瘤抑制基因如TP53、Rb和PTEN发生突变或缺失，导致基因组不稳定和更具侵袭性的表型。采用目前可用的治疗策略，晚期疾病的生存率较低。在对人类癌症进行分子特征分析的能力方面取得的技术进步，已导致发现了可能具有治疗价值的基因改变。新型化疗药物，如抗叶酸剂和紫杉烷类，已在尿路上皮癌中显示出前景。针对新型分子靶点的药物，如人表皮受体（HER）和血管内皮生长因子受体（VEGFR），正在进行研究。这篇综述文章重点关注新型化疗药物和靶向药物以及目前正在浸润性尿路上皮癌临床开发中的免疫疗法的现状。
