Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
Med Res Rev. 2019 Jul;39(4):1398-1426. doi: 10.1002/med.21568. Epub 2019 Feb 11.
Microtubule (MT)-targeting agents are highly successful drugs as chemotherapeutic agents, and this is attributed to their ability to target MT dynamics and interfere with critical cellular functions, including, mitosis, cell signaling, intracellular trafficking, and angiogenesis. Because MT dynamics vary in the different stages of the cell cycle, these drugs tend to be the most effective against mitotic cells. While this class of drug has proven to be effective against many cancer types, significant hurdles still exist and include overcoming aspects such as dose limited toxicities and the development of resistance. Newer generations of developed drugs attack these problems and alternative approaches such as the development of dual tubulin and kinase inhibitors are being investigated. This approach offers the potential to show increased efficacy and lower toxicities. This review covers different categories of MT-targeting agents, recent advances in dual inhibitors, and current challenges for this drug target.
微管（MT）靶向剂作为化疗药物非常成功，这归因于它们靶向 MT 动力学和干扰关键细胞功能的能力，包括有丝分裂、细胞信号转导、细胞内运输和血管生成。由于 MT 动力学在细胞周期的不同阶段有所不同，这些药物往往对有丝分裂细胞最有效。虽然这类药物已被证明对许多癌症类型有效，但仍然存在重大障碍，包括克服剂量限制毒性和耐药性的发展等方面。新一代开发的药物解决了这些问题，并且正在研究双重微管和激酶抑制剂等替代方法。这种方法有可能显示出更高的疗效和更低的毒性。本综述涵盖了 MT 靶向剂的不同类别、双重抑制剂的最新进展以及该药物靶点的当前挑战。
