Mechanisms of enzalutamide resistance in castration‐resistant prostate cancer and therapeutic strategies to overcome it

作者：Yuanyuan Wang, Jiyuan Chen, Zhengjie Wu, Weihong Ding, Shen Gao, Yuan Gao, Chuanliang Xu · 发表于：British Journal of Pharmacology · 年份：2020 · DOI：10.1111/bph.15300 · 被引用次数：111 · 研究领域：Prostate Cancer Treatment and Research、Cancer, Lipids, and Metabolism、Estrogen and related hormone effects

Prostate cancer is the second most common malignancy in men and androgen deprivation therapy is the first-line therapy. However, most cases will eventually develop castration-resistant prostate cancer after androgen deprivation therapy treatment. Enzalutamide is a second-generation androgen receptor antagonist approved by the Food and Drug Administration to treat patients with castration-resistant prostate cancer. Unfortunately, patients receiving enzalutamide treatment will ultimately develop resistance via various complicated mechanisms. This review examines the emerging information on these resistance mechanisms, including androgen receptor-related signalling pathways, glucocorticoid receptor-related pathways and metabolic effects. Notably, lineage plasticity and phenotype switching, gene polymorphisms and the relationship between microRNAs and drug resistance are addressed. Furthermore, potential therapeutic strategies for enzalutamide-resistant castration-resistant prostate cancer treatment are suggested, which can help discover more effective and specific regimens to overcome enzalutamide resistance.