Improving Taxane-Based Chemotherapy in Castration-Resistant Prostate Cancer

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.

TrendsPreclinical evidence establishes the therapeutic potential of reverting resistance mechanisms in docetaxel-resistant prostate cancer cells.Targeted drug delivery of taxanes has the potential to enhance the antitumor efficacy, enhance tolerability, and permit the administration of intensified dosages.Changes in levels of circulating tumor cells are indicative of responses to docetaxel treatment and can be further characterized to provide robust predictive markers for personalized treatment.