Department of Obstetrics, Gynecology and Reproductive Sciences, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
Drug Resist Updat. 2022 Dec;65:100881. doi: 10.1016/j.drup.2022.100881. Epub 2022 Oct 15.
Taxanes (Taxol/paclitaxel, Docetaxel/taxotere) are a key group of successful drugs commonly used in chemotherapy to treat several major malignant tumors also as a front-line agent in combination with carboplatin/cisplatin, as well as a second line drug with a dose dense regimen following recurrence. Overall, the response to paclitaxel is excellent, though drug resistance inevitably develops in subsequent treatments. The commonly accepted mechanism of action is that the hindrance of microtubule function by paclitaxel leads to cell cycle arrest at mitosis, and subsequent apoptosis. The mechanisms for resistance to paclitaxel have also been extensively investigated, such as ABC transporter overexpression, altered signaling and apoptotic gene expression to resist cell death, and changes associated with microtubules to reduce influences of the drugs. Meanwhile, another important mechanism of paclitaxel resistance has been proposed: increased nuclear lamina/envelope sturdiness to retard the breaking of nuclear envelop and the paclitaxel-induced multinucleation as well as the formation of multiple micronuclei. Here in this review, we focus on experimental findings and ideas on the mechanism of paclitaxel resistance related to cancer nuclear envelope, to provide new insights on overcoming paclitaxel resistance.
紫杉醇类（紫杉醇/紫杉醇、多西紫杉醇/紫杉醇特）是一组成功的药物，常用于化疗治疗几种主要恶性肿瘤，也作为联合卡铂/顺铂的一线药物，以及在复发后采用密集剂量方案的二线药物。总的来说，紫杉醇的反应非常好，尽管在随后的治疗中不可避免地会产生耐药性。公认的作用机制是紫杉醇对微管功能的阻碍导致细胞周期在有丝分裂时停滞，并随后发生细胞凋亡。对紫杉醇耐药的机制也进行了广泛的研究，如 ABC 转运蛋白过度表达、改变信号和凋亡基因表达以抵抗细胞死亡，以及与微管相关的变化以减少药物的影响。同时，提出了紫杉醇耐药的另一个重要机制：增加核层/包膜的坚固性以延缓核包膜的破裂以及紫杉醇诱导的多核形成和多个微核的形成。在这篇综述中，我们重点关注与癌症核包膜相关的紫杉醇耐药机制的实验发现和观点，为克服紫杉醇耐药提供新的见解。
