Wilson Richard H
Centre for Cancer Research and Cell Biology, Queen's University, Belfast, Northern Ireland, UK.
Oncologist. 2006 Oct;11(9):1018-24. doi: 10.1634/theoncologist.11-9-1018.
Developments that may improve existing cytotoxic therapy for colorectal cancer (CRC) include alternatives to 5-fluorouracil (5-FU) such as the liposomal Thymidylate Synthase inhibitor OSI-7904L and the multitargeted antifolate pemetrexed. Studies have explored means of reformulating irinotecan, modulating its pharmacokinetics, and enhancing its activity by maximizing DNA damage through poly(ADP-ribose) polymerase inhibition. Cell cycle inhibitors may offer an alternative to combination with 5-FU. However, as standard regimens become more complex, so do the clinical trials needed to develop new agents, and the path to registration becomes ever more tortuous. It is therefore likely that several drugs with promise in CRC will not be developed for this indication.
可能改善现有结直肠癌（CRC）细胞毒性疗法的进展包括5-氟尿嘧啶（5-FU）的替代物，如脂质体胸苷酸合成酶抑制剂OSI-7904L和多靶点抗叶酸药物培美曲塞。研究探索了重新配制伊立替康的方法，调节其药代动力学，并通过抑制聚（ADP-核糖）聚合酶使DNA损伤最大化来增强其活性。细胞周期抑制剂可能提供一种替代与5-FU联合使用的方法。然而，随着标准治疗方案变得更加复杂，开发新药物所需的临床试验也变得更加复杂，注册之路也变得更加曲折。因此，几种在CRC中有前景的药物可能不会针对该适应症进行开发。
