Abstract
Prostate cancer (PCa) is the second most common malignancy in men, and
androgen deprivation therapy (ADT) is the first-line therapy. However,
most cases will eventually develop into castration-resistant prostate
cancer (CRPC) after ADT treatment. Enzalutamide (Enz) is a
second-generation androgen receptor inhibitor approved by the Food and
Drug Administration to treat patients with CRPC. Unfortunately, patients
receiving Enz treatment will ultimately develop resistance via various
complicated mechanisms. In this review, we introduce the emerging
information on resistance mechanisms, including androgen
receptor-related signalling pathways, glucocorticoid receptor-related
pathways, and metabolic mechanisms. Notably, lineage plasticity and
phenotype switching, gene polymorphisms, and the relationship between
microRNAs and drug resistance are addressed. Furthermore, potential
therapeutic strategies for Enz-resistant CRPC treatment are suggested,
which can help in the discovery of more effective and specific regimens
to overcome Enz resistance.