Castration-Resistant Prostate Cancer: From Uncovered Resistance Mechanisms to Current Treatments

SIMPLE SUMMARY: Castration-resistant prostate cancer (CRPC) remains a significant medical challenge, even with recent advancements in diagnosis and treatment. To improve patient outcomes, it is important to understand the underlying mechanisms of resistance to treatments and develop new therapeutic approaches. This review provides a brief summary of the current knowledge on the mechanisms that contribute to CRPC progression, including both androgen receptor (AR)-dependent and AR-independent pathways. It also discusses approved and currently investigated treatment options to treat patients with CRPC, such as novel chemotherapies, radiation therapy, immunotherapy, PARP inhibitors, and potential combined therapeutic strategies. ABSTRACT: Prostate cancer (PC) is the second most common cancer in men worldwide. Despite recent advances in diagnosis and treatment, castration-resistant prostate cancer (CRPC) remains a significant medical challenge. Prostate cancer cells can develop mechanisms to resist androgen deprivation therapy, such as AR overexpression, AR mutations, alterations in AR coregulators, increased steroidogenic signaling pathways, outlaw pathways, and bypass pathways. Various treatment options for CRPC exist, including androgen deprivation therapy, chemotherapy, immunotherapy, localized or systemic therapeutic radiation, and PARP inhibitors. However, more research is needed to combat CRPC effectively. Further investigation into the underlying mechanisms of the disease and the development of new therapeutic strategies will be crucial in improving patient outcomes. The present work summarizes the current knowledge regarding the underlying mechanisms that promote CRPC, including both AR-dependent and independent pathways. Additionally, we provide an overview of the currently approved therapeutic options for CRPC, with special emphasis on chemotherapy, radiation therapy, immunotherapy, PARP inhibitors, and potential combination strategies.