Škubník Jan, Svobodová Pavlíčková Vladimíra, Ruml Tomáš, Rimpelová Silvie
Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Technická 3, Prague 6 166 28, Czech Republic.
Biomed Pharmacother. 2023 May;161:114458. doi: 10.1016/j.biopha.2023.114458. Epub 2023 Mar 6.
Paclitaxel, a compound naturally occurring in yew, is a commonly used drug for the treatment of different types of cancer. Unfortunately, frequent cancer cell resistance significantly decreases its anticancer effectivity. The main reason for the resistance development is the paclitaxel-induced phenomenon of cytoprotective autophagy occurring by different mechanisms of action in dependence on a cell type and possibly even leading to metastases. Paclitaxel also induces autophagy in cancer stem cells, which greatly contributes to tumor resistance development. Paclitaxel anticancer effectivity can be predicted by the presence of several autophagy-related molecular markers, such as tumor necrosis factor superfamily member 13 in triple-negative breast cancer or cystine/glutamate transporter encoded by the SLC7A11 gene in ovarian cancer. Nevertheless, the undesired effects of paclitaxel-induced autophagy can be eliminated by paclitaxel co-administration with autophagy inhibitors, such as chloroquine. Interestingly, in certain cases, it is worthy of potentiating autophagy by paclitaxel combination with autophagy inducers, for instance, apatinib. A modern strategy in anticancer research is also to encapsulate chemotherapeutics into nanoparticle carriers or develop their novel derivatives with improved anticancer properties. Hence, in this review article, we summarize not only the current knowledge of paclitaxel-induced autophagy and its role in cancer resistance but mainly the possible drug combinations based on paclitaxel and their administration in nanoparticle-based formulations as well as paclitaxel analogs with autophagy-modulating properties.
紫杉醇是一种天然存在于紫杉中的化合物，是治疗不同类型癌症的常用药物。不幸的是，癌细胞频繁产生耐药性会显著降低其抗癌效果。耐药性产生的主要原因是紫杉醇诱导的细胞保护性自噬现象，其通过不同的作用机制发生，这取决于细胞类型，甚至可能导致转移。紫杉醇还会在癌症干细胞中诱导自噬，这对肿瘤耐药性的发展有很大影响。紫杉醇的抗癌效果可以通过几种自噬相关分子标志物的存在来预测，比如三阴性乳腺癌中的肿瘤坏死因子超家族成员13或卵巢癌中由SLC7A11基因编码的胱氨酸/谷氨酸转运体。然而，紫杉醇诱导的自噬的不良影响可以通过将紫杉醇与自噬抑制剂（如氯喹）联合使用来消除。有趣的是，在某些情况下，将紫杉醇与自噬诱导剂（如阿帕替尼）联合使用来增强自噬是值得的。抗癌研究中的一种现代策略也是将化疗药物封装到纳米颗粒载体中，或者开发具有改善抗癌特性的新型衍生物。因此，在这篇综述文章中，我们不仅总结了目前关于紫杉醇诱导的自噬及其在癌症耐药性中的作用的知识，而且主要总结了基于紫杉醇的可能的药物组合及其在基于纳米颗粒的制剂中的给药方式，以及具有自噬调节特性的紫杉醇类似物。
