Sarfaty Michal, Rosenberg Jonathan E
Department of Medicine, Division of Solid Tumor Oncology, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, USA.
Oncology Department, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, Israel.
Curr Oncol Rep. 2020 Feb 1;22(2):13. doi: 10.1007/s11912-020-0879-y.
Urothelial carcinoma (UC) is a common malignancy with an urgent need for more effective and less toxic treatment strategies. Antibody-drug conjugate (ADC) represents a novel therapeutic approach, which combines the high specificity of monoclonal antibodies covalently linked with highly active cytotoxic agents. UC is an appropriate candidate for these drugs, as it expresses unique cell surface antigens that allow for specific targeting of these cells. We hereby present a review of the current literature and future perspectives of ADC treatment in early-stage and metastatic UC.
Several ADCs are in advanced stages of development and approval, such as intravesical oportuzumab monatox in BCG-refractory non-muscle invasive bladder cancer and enfortumab vedotin and sacituzumab govitecan in pretreated metastatic UC. Other agents are in earlier stages of development, including some promising anti-Her2 agents. The favorable toxicity profile of these agents led to several combination strategies, especially with checkpoint inhibitors. In light of the encouraging results presented in this review and the recent FDA approval of enfortumab vedotin, ADCs will likely be incorporated in the management of UC in the near future.
尿路上皮癌(UC)是一种常见的恶性肿瘤,迫切需要更有效且毒性更小的治疗策略。抗体药物偶联物(ADC)代表了一种新型治疗方法,它将单克隆抗体的高特异性与高活性细胞毒性药物共价连接。UC是这些药物的合适候选者,因为它表达独特的细胞表面抗原,能够实现对这些细胞的特异性靶向。我们在此对ADC治疗早期和转移性UC的当前文献及未来前景进行综述。
几种ADC正处于开发和审批的后期阶段,如用于卡介苗难治性非肌层浸润性膀胱癌的膀胱内注射oportuzumab monatox,以及用于经治转移性UC的enfortumab vedotin和sacituzumab govitecan。其他药物正处于早期开发阶段,包括一些有前景的抗Her2药物。这些药物良好的毒性特征促成了多种联合策略,尤其是与检查点抑制剂联合。鉴于本综述中呈现的令人鼓舞的结果以及美国食品药品监督管理局(FDA)最近对enfortumab vedotin的批准,ADC在不久的将来可能会被纳入UC的治疗管理中。