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

Cancers (Basel). 2023 Oct 19;15(20):5047. doi: 10.3390/cancers15205047.

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.

Keywords: PARP inhibitors; androgen deprivation therapy (ADT); androgen signaling; castration-resistant prostate cancer; chemotherapy; immunotherapy; radionuclide therapy.

Publication types

  • Review

Grants and funding

This work was supported by INSERM and grants from the La Ligue (R22030AA), Association pour la Recherche sur les Tumeurs de la Prostate (ARTP) and La Fondation A*Midex -2021 AAP Interdisciplinarité. T.K.L.’s postdoc fellowship was funded by ITMO Cancer (C21033AS). Q.H.D.’s doctoral fellowship was funded by the France Excellence scholarship.