Leiden University Medical Center, Department of Urology, J-3-100, Albinusdreef 2, Leiden, The Netherlands.
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Trends Pharmacol Sci. 2016 Jun;37(6):451-462. doi: 10.1016/j.tips.2016.03.003. Epub 2016 Apr 8.
Currently, the clinical utility of taxane-based drug formulations in castration-resistant prostate cancer (CRPC) is severely limited by acquired chemotherapy resistance, dose-limiting toxicities, and nonresponders. Therefore, approaches to improve taxane-based chemotherapy are desperately required. In this review, we highlight the strategies that aim to overcome these limitations, such as bypassing therapy resistance, targeted drug delivery, and adequate prediction of therapy response. The involvement of the apoptotic pathway, ABC transporters, the glucocorticoid receptor (GR) axis, androgen receptor (AR) splicing, epithelial plasticity, and cancer stem cells in mediating taxane-resistance are outlined. Furthermore, passive and active targeted nanomedicinal drug delivery strategies and the use of circulating tumor cells in predicting docetaxel responses are discussed. Finally, recent advances towards clinical translation of these approaches in CRPC are reviewed.
目前，基于紫杉烷的药物制剂在去势抵抗性前列腺癌（CRPC）中的临床应用受到获得性化疗耐药性、剂量限制性毒性和无应答者的严重限制。因此，迫切需要改进基于紫杉烷的化疗方法。在这篇综述中，我们强调了旨在克服这些限制的策略，例如绕过治疗耐药性、靶向药物递送以及充分预测治疗反应。概述了凋亡途径、ABC 转运体、糖皮质激素受体（GR）轴、雄激素受体（AR）剪接、上皮可塑性和癌症干细胞在介导紫杉烷耐药性中的作用。此外，还讨论了被动和主动靶向纳米药物递送策略以及循环肿瘤细胞在预测多西紫杉醇反应中的应用。最后，回顾了这些方法在 CRPC 中临床转化的最新进展。
