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Mechanisms of enzalutamide resistance in castration‐resistant prostate cancer and therapeutic strategies to overcome it
Author(s) -
Wang Yuanyuan,
Chen Jiyuan,
Wu Zhengjie,
Ding Weihong,
Gao Shen,
Gao Yuan,
Xu Chuanliang
Publication year - 2021
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15300
Subject(s) - enzalutamide , prostate cancer , androgen deprivation therapy , medicine , androgen receptor , androgen , oncology , cancer , cancer research , hormone
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.