Škubník Jan, Pavlíčková Vladimíra, Ruml Tomáš, Rimpelová Silvie
Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technická 3, 166 28 Prague 6, Czech Republic.
Plants (Basel). 2021 Mar 17;10(3):569. doi: 10.3390/plants10030569.
Taxanes, mainly paclitaxel and docetaxel, the microtubule stabilizers, have been well known for being the first-line therapy for breast cancer for more than the last thirty years. Moreover, they have been also used for the treatment of ovarian, hormone-refractory prostate, head and neck, and non-small cell lung carcinomas. Even though paclitaxel and docetaxel significantly enhance the overall survival rate of cancer patients, there are some limitations of their use, such as very poor water solubility and the occurrence of severe side effects. However, this is what pushes the research on these microtubule-stabilizing agents further and yields novel taxane derivatives with significantly improved properties. Therefore, this review article brings recent advances reported in taxane research mainly in the last two years. We focused especially on recent methods of taxane isolation, their mechanism of action, development of their novel derivatives, formulations, and improved tumor-targeted drug delivery. Since cancer cell chemoresistance can be an unsurpassable hurdle in taxane administration, a significant part of this review article has been also devoted to combination therapy of taxanes in cancer treatment. Last but not least, we summarize ongoing clinical trials on these compounds and bring a perspective of advancements in this field.
紫杉烷类，主要是紫杉醇和多西他赛，作为微管稳定剂，在过去三十多年里一直是乳腺癌的一线治疗药物。此外，它们还被用于治疗卵巢癌、激素难治性前列腺癌、头颈癌和非小细胞肺癌。尽管紫杉醇和多西他赛显著提高了癌症患者的总生存率，但它们的使用存在一些局限性，比如水溶性很差以及会出现严重的副作用。然而，正是这些促使对这些微管稳定剂的研究进一步深入，并产生了性能显著改善的新型紫杉烷衍生物。因此，这篇综述文章介绍了紫杉烷研究，主要是近两年来报道的最新进展。我们特别关注了紫杉烷分离的最新方法、它们的作用机制、新型衍生物的开发、制剂以及改进的肿瘤靶向药物递送。由于癌细胞的化疗耐药性可能是紫杉烷给药中无法逾越的障碍，这篇综述文章的很大一部分内容也致力于紫杉烷在癌症治疗中的联合疗法。最后但同样重要的是，我们总结了这些化合物正在进行的临床试验，并展望了该领域的进展。
