Anticancer Molecular Oncology Laboratory, College of Veterinary Medicine, The University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA.
Nat Rev Urol. 2011 Oct 4;8(11):608-16. doi: 10.1038/nrurol.2011.135.
Urinary bladder cancer is the fifth most common cancer in the US and the most costly cancer to manage because it requires life-long surveillance to monitor for recurrence and advanced progression. Urothelial carcinomas account for more than 90% of urinary bladder cancer cases. Transurethral resection and intravesical chemotherapy or immunotherapy are effective short-term treatments of urothelial carcinoma, but long-term management has not yet been optimized. Recent therapeutic strategies emphasize the targeted interference with aberrantly-regulated signaling modulators that result from genomic alterations. However, targeted therapeutic agents might not distinguish cancer cells from their normal counterparts, resulting in undesirable adverse effects. Thus, a new approach for the treatment of urothelial carcinoma has been suggested that differentially augments cancer-associated events, leading to selective death of cancer cells but not normal cells. Many aberrantly-regulated signaling modulators are associated with the elevation of reactive oxygen species (ROS), and an increasing number of studies report agents with the ability to induce ROS in cancer cells. Accordingly, therapeutic augmentation of ROS to a lethal level in cancer cells only would induce selective death of tumor cells but not normal cells, leading to a highly effective chemotherapy strategy for urothelial carcinoma.
膀胱癌是美国第五大常见癌症，也是治疗费用最高的癌症，因为它需要终身监测以监测复发和进展。尿路上皮癌占膀胱癌病例的 90%以上。经尿道膀胱肿瘤切除术和膀胱内化疗或免疫治疗是治疗尿路上皮癌的有效短期治疗方法，但长期管理尚未得到优化。最近的治疗策略强调靶向干预由于基因组改变而导致的异常调节信号调节剂。然而，靶向治疗药物可能无法区分癌细胞与其正常细胞，从而导致不良的不良反应。因此，已经提出了一种治疗尿路上皮癌的新方法，该方法可选择性地增强与癌症相关的事件，导致癌细胞选择性死亡而不会导致正常细胞死亡。许多异常调节的信号调节剂与活性氧（ROS）的升高有关，越来越多的研究报告了具有在癌细胞中诱导 ROS 的能力的药物。因此，仅将 ROS 增强到癌细胞中的致死水平将诱导肿瘤细胞选择性死亡而不会导致正常细胞死亡，从而为尿路上皮癌提供了一种非常有效的化疗策略。
