About this Research Topic
Androgen-deprivation therapy (ADT) has been the mainstay therapy for patients with advanced prostate cancer, but inevitably the disease will progress to castration-resistant prostate cancer (CRPC) in a median duration of 2 years. Yet, CRPC is still largely dependent on androgen receptor signaling. Second-generation ADT (abiraterone and enzalutamide) and chemotherapy (docetaxel and cabazitaxel) are effective in a subset of patients, but responding tumors eventually develop resistance. Consistent with the heterogenous nature of CRPC, mechanisms underlying de novo and acquired resistance are largely diverse. Recent studies have highlighted potential resistance mechanisms to second-generation ADT including androgen receptor splicing, adaptive/enhanced androgen receptor signaling, altered NFkB signaling, perturbed lipid metabolism, neuroendocrine differentiation, and genetic mutation in cell survival pathways. Resistance to chemotherapy has been associated with an increased drug efflux. With the increasing introduction of second-generation ADT in neoadjuvant settings, the biology underpinning the emerging CRPC will be of immense interest. Identifying treatment resistant mechanisms will provide critical information for the development of next-line therapy.
Alhtough new therapies have significantly benefited patients who respond to the treatments, a subset of patients does not respond. Understanding why a subset of patient responds or identifying biomarkers to select patients who may respond to a specific therapy will direct effective treatment. Furthermore, exploring markers to detect early relapse will offer options for patients to discuss alternative treatments and allow optimization of personalized sequential therapy.
Keywords: Androgen receptor, androgen deprivation, abiraterone, enzalutamide, neuroendocrine
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