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Review
. 2021 Jan;178(2):239-261.
doi: 10.1111/bph.15300. Epub 2020 Dec 14.

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

Yuanyuan Wang  1 , Jiyuan Chen  1 , Zhengjie Wu  2 , Weihong Ding  3 , Shen Gao  2 , Yuan Gao  1 , Chuanliang Xu  2
Affiliations
Free article
Review

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

Yuanyuan Wang et al. Br J Pharmacol. 2021 Jan.
Free article

Abstract

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.

Keywords: castration-resistant prostate cancer; enzalutamide; prostate cancer; resistance.

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