Section of Oncology & Clinical Research, Leeds Institute of Molecular Medicine, St. James' Institute of Oncology, St. James' University Hospital, Leeds, UK.
Future Med Chem. 2013 Mar;5(3):339-52. doi: 10.4155/fmc.12.217.
Anticancer drugs directed against the microtubule, including taxanes and vinca alkaloids, have been the backbone of many chemotherapy regimes for decades. These drugs have, however, significant limitations, which have prompted the development of novel microtubule targeting agents (MTAs). This article will discuss MTAs for anticancer therapies and recent debates regarding their mechanisms of action. Furthermore, the limitations of taxanes, including hypersensitivity reactions, neurotoxicity, drug resistance and lack of validated biomarkers to guide therapy will be discussed, all of which have driven the development of novel agents. The mechanisms of action and drug development of new generations of MTAs will also be outlined. Agents demonstrating utility in Phase III clinical trials, including eribulin, ixabepilone, cabazitaxel and trastuzumab-DM1 will be highlighted, as well as novel agents currently in development and future directions for MTAs.
几十年来,针对微管的抗癌药物,包括紫杉醇类和长春碱类生物碱,一直是许多化疗方案的基础。然而,这些药物有很大的局限性,这促使了新型微管靶向药物(MTAs)的发展。本文将讨论用于癌症治疗的 MTAs 以及最近关于其作用机制的争论。此外,还将讨论紫杉醇类药物的局限性,包括过敏反应、神经毒性、耐药性和缺乏有效的生物标志物来指导治疗,所有这些都推动了新型药物的发展。还将概述新一代 MTAs 的作用机制和药物开发。将重点介绍在 III 期临床试验中显示出疗效的药物,包括艾日布林、伊沙匹隆、卡巴他赛和曲妥珠单抗-DM1,以及目前正在开发的新型药物和 MTAs 的未来方向。