Epothilones: Mechanism of action and biologic activity
Epothilones: Mechanism of action and biologic activity
复制标题
DOI：
10.1200/jco.2004.12.001
复制
发表时间：
2004-05-15
影响因子：
45.3
通讯作者：
Rubin, EH
中科院分区：
文献类型：
--
作者：
Goodin, S;Kane, MP;Rubin, EH
针对微管的药物是最常用的抗癌药物之一。尽管微管功能的干扰导致癌细胞选择性死亡的机制尚不清楚，但几种新的微管靶向化合物正在进行临床试验。在某种程度上，这些努力的重点是克服与紫杉烷为基础的治疗相关的一些问题，包括配方和给药困难和p -糖蛋白引起的耐药易感性。从这些努力中，埃泊霉素成为了一种很有前途的新型抗癌药物。临床前研究表明，艾泊霉素与微管结合和稳定的方式与紫杉醇相似，但不完全相同，并且艾泊霉素在紫杉醇耐药肿瘤模型中有效。BMS-247550、BMS-310705、EPO906和KOS-862的临床I期和早期11期数据均可获得。结果表明，这些化合物具有广泛的抗肿瘤活性，剂量和时间表与可耐受的副作用相关。
Drugs that target microtubules are among the most commonly prescribed anticancer therapies. Although the mechanisms by which perturbation of microtubule function leads to selective death of cancer cells remain unclear, several new microtubule-targeting compounds are undergoing clinical testing. In part, these efforts focus on overcoming some of the problems associated with taxane-based therapies, including formulation and administration difficulties and susceptibility to resistance conferred by P-glycoprotein. Epothilones have emerged from these efforts as a promising new class of anticancer drugs. Preclinical studies indicate that epothilones bind to and stabilize microtubules in a manner similar but not identical to that of paclitaxel and that epothilones are effective in paclitaxel-resistant tumor models. Clinical phase I and early phase 11 data are available for BMS-247550, BMS-310705, EPO906, and KOS-862. The results suggest that these compounds have a broad range of antitumor activity at doses and schedules associated with tolerable side effects.