Since 1984, when paclitaxel was approved by the FDA for the treatment of advanced ovarian carcinoma, taxanes have been widely used as microtubule-targeting antitumor agents. However, their historic classification as antimitotics does not describe all their functions. Indeed, taxanes act in a complex manner, altering multiple cellular oncogenic processes including mitosis, angiogenesis, apoptosis, inflammatory response, and ROS production. On the one hand, identification of the diverse effects of taxanes on oncogenic signaling pathways provides opportunities to apply these cytotoxic drugs in a more rational manner. On the other hand, this may facilitate the development of novel treatment modalities to surmount anticancer drug resistance. In the latter respect, chemoresistance remains a major impediment which limits the efficacy of antitumor chemotherapy. Taxanes have shown impact on key molecular mechanisms including disruption of mitotic spindle, mitosis slippage and inhibition of angiogenesis. Furthermore, there is an emerging contribution of cellular processes including autophagy, oxidative stress, epigenetic alterations and microRNAs deregulation to the acquisition of taxane resistance. Hence, these two lines of findings are currently promoting a more rational and efficacious taxane application as well as development of novel molecular strategies to enhance the efficacy of taxane-based cancer treatment while overcoming drug resistance.

This review provides a general and comprehensive picture on the use of taxanes in cancer treatment. In particular, we describe the history of application of taxanes in anticancer therapeutics, the synthesis of the different drugs belonging to this class of cytotoxic compounds, their features and the differences between them. We further dissect the molecular mechanisms of action of taxanes and the molecular basis underlying the onset of taxane resistance. We further delineate the possible modalities to overcome chemoresistance to taxanes, such as increasing drug solubility, delivery and pharmacokinetics, overcoming microtubule alterations or mitotic slippage, inhibiting drug efflux pumps or drug metabolism, targeting redox metabolism, immune response, and other cellular functions.

自 1984 年紫杉醇被 FDA 批准用于治疗晚期卵巢癌以来，紫杉烷类药物被广泛用作微管靶向抗肿瘤药物。然而，它们作为抗有丝分裂剂的历史分类并没有描述它们的所有功能。事实上，紫杉烷以复杂的方式起作用，改变多种细胞致癌过程，包括有丝分裂、血管生成、细胞凋亡、炎症反应和 ROS 产生。一方面，确定紫杉烷对致癌信号通路的不同影响为以更合理的方式应用这些细胞毒性药物提供了机会。另一方面，这可能有助于开发新的治疗方式以克服抗癌药物耐药性。在后者方面，化学抗性仍然是限制抗肿瘤化学疗法功效的主要障碍。紫杉烷已显示出对关键分子机制的影响，包括有丝分裂纺锤体的破坏、有丝分裂的滑动和血管生成的抑制。此外，包括自噬、氧化应激、表观遗传改变和 microRNA 失调在内的细胞过程对紫杉烷抗性的获得有新的贡献。因此，这两条线的发现目前正在促进更合理和有效的紫杉烷应用，以及开发新的分子策略，以提高基于紫杉烷的癌症治疗的疗效，同时克服耐药性。包括自噬、氧化应激、表观遗传改变和 microRNA 失调在内的细胞过程对紫杉烷抗性的获得做出了新的贡献。因此，这两条线的发现目前正在促进更合理和有效的紫杉烷应用，以及开发新的分子策略，以提高基于紫杉烷的癌症治疗的疗效，同时克服耐药性。包括自噬、氧化应激、表观遗传改变和 microRNA 失调在内的细胞过程对紫杉烷抗性的获得做出了新的贡献。因此，这两条线的发现目前正在促进更合理和有效的紫杉烷应用，以及开发新的分子策略，以提高基于紫杉烷的癌症治疗的疗效，同时克服耐药性。

这篇综述提供了关于紫杉烷在癌症治疗中的使用的一般和全面的图片。我们特别介绍了紫杉烷类在抗癌治疗中的应用历史、属于此类细胞毒性化合物的不同药物的合成、它们的特征以及它们之间的差异。我们进一步剖析了紫杉烷作用的分子机制和紫杉烷抗性发生的分子基础。我们进一步描绘了克服紫杉烷类化学抗性的可能方式，例如增加药物溶解度、递送和药代动力学、克服微管改变或有丝分裂滑脱、抑制药物外排泵或药物代谢、靶向氧化还原代谢、免疫反应和其他细胞功能。