Targeting the microtubules in breast cancer beyond taxanes: The epothilones
Targeting the microtubules in breast cancer beyond taxanes: The epothilones
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DOI：
10.1634/theoncologist.12-3-271
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发表时间：
2007-01-01
期刊：
影响因子：
5.8
通讯作者：
Baselga, Jose
中科院分区：
文献类型：
--
作者：
Cortes, Javier;Baselga, Jose
微管靶向药物如紫杉烷类对乳腺癌具有高度活性，已成为治疗早期和晚期乳腺癌患者的基石。天然埃博霉素及其类似物是一类新型的微管稳定剂，其结合微管蛋白并导致凋亡性细胞死亡。在这类化合物中，帕土匹隆、伊沙匹隆、BMS-310705、ZK-EPO和科斯-862处于临床开发中。广泛的临床前研究表明，埃博霉素是通过与紫杉烷部分非重叠的作用机制。在临床上，在一系列I期和II期研究中发现埃博霉素即使在最近进展为紫杉烷类的患者中也是有效的。这些药物的毒性主要包括感觉神经病变，有时是可逆的。已经进行了埃博霉素的新辅助研究，一些晚期乳腺癌的III期研究正在进行或最近已经完成。这些研究的结果是热切期待的，预计埃博霉素可能成为乳腺癌患者的一个重要治疗选择。
Microtubule-targeting agents such as the taxanes are highly active against breast cancer and have become a cornerstone in the treatment of patients with early and advanced breast cancer. The natural epothilones and their analogs are a novel class of microtubule-stabilizing agents that bind tubulin and result in apoptotic cell death. Among this family of compounds, patupilone, ixabepilone, BMS-310705, ZK-EPO, and KOS-862 are in clinical development. Extensive preclinical studies have shown that epothilones are working through partially nonoverlapping mechanisms of action with taxanes. In the clinic, epothilones have been found in a series of phase I and phase II studies to be active even in patients who had recently progressed to taxanes. The toxicity profile of these agents consists mostly of sensory neuropathy, sometimes reversible. Neoadjuvant studies with epothilones have been conducted and a number of phase III studies in advanced breast cancer are either under way or have been recently completed. The results of these studies are eagerly awaited and it is anticipated that epothilones may become an important treatment option in patients with breast cancer.