Metastatic Castration-Resistant Prostate Cancer: Insights on Current Therapy and Promising Experimental Drugs

Abstract

The therapeutic landscape of metastatic hormone sensitive and metastatic castration-resistant prostate cancer (mCRPC) is rapidly changing. We reviewed the current treatment options for mCRPC, with insights on new available therapeutic strategies. Chemotherapy with docetaxel or cabazitaxel (for patients progressing on docetaxel), as well as treatment with androgen receptor axis targeted therapies, and Radium-223 are well-established treatment options for patients with mCRPC. The advent of theragnostic in prostate cancer established Lutetium-177 (177Lu)-PSMA-617 as a new standard of care for PSMA-positive mCRPC previously treated with ARAT and taxane-based chemotherapy. Olaparib, a poly-ADP-ribose polymerase (PARP) inhibitor, is approved for selected patients with mCRPC progressed on ARATs and in combination with abiraterone acetate as first-line treatment for mCRPC. Immunotherapy showed limited efficacy in unselected patients with mCRPC and novel immunotherapy strategies need to be explored. The search for biomarkers is a growing field of interest in mCRPC, and predictive biomarkers are needed to support the choice of treatment and the development of tailored strategies.

Addressing the risk and management of cardiometabolic complications in prostate cancer patients on androgen deprivation therapy and androgen receptor axis-targeted therapy: consensus statements from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology

“…MI, stroke, heart failure, and CV mortality) as primary endpoints, adequately powered statistical plans, and balanced baseline patient characteristics regarding prior CVDs and CV risk factors between treatment arms. Fourth, the potential for cardiotoxicity of newer therapies for mCRPC, such as poly-ADP-ribose polymerase inhibitors, should be further assessed and monitored ( 86 , 87 ).…”

Plasma microRNA Signature as Companion Diagnostic for Abiraterone Acetate Treatment in Metastatic Castration-Resistant Prostate Cancer: A Pilot Study

“…The evolving therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) over the last decade has represented a challenge for clinicians, who must navigate through various treatment options [ 21 ]. However, given that all patients eventually develop primary or acquired resistance to available drugs, the urgent need for effective biomarkers to identify individuals who are most likely to benefit from specific treatments is crucial.…”

“…While early stage PCa is often responsive to androgen deprivation [ 20 ], advanced stages may develop resistance to this treatment, a phenomenon termed castration-resistant prostate cancer (CRPC). The treatment landscape for metastatic CRPC (mCRPC) has evolved significantly, with several agents approved for clinical use in the US and Europe, demonstrating improved survival rates in both treatment-naïve and previously treated mCRPC patients [ 21 ]. Among these strategies, abiraterone acetate (AA), a cytochrome P450 c17 (CYP17A) inhibitor, has shown efficacy in mCRPC patients, including those who have received chemotherapy [ 21 , 22 ].…”

“…The treatment landscape for metastatic CRPC (mCRPC) has evolved significantly, with several agents approved for clinical use in the US and Europe, demonstrating improved survival rates in both treatment-naïve and previously treated mCRPC patients [ 21 ]. Among these strategies, abiraterone acetate (AA), a cytochrome P450 c17 (CYP17A) inhibitor, has shown efficacy in mCRPC patients, including those who have received chemotherapy [ 21 , 22 ]. AA functions by inhibiting testosterone production from testicular, adrenal, and prostate cancer tissues [ 23 ].…”

Integrative Metabolomic Analysis of Serum and Selected Serum Exosomal microRNA in Metastatic Castration-Resistant Prostate Cancer

“…There is also an increasing focus on the MRI-guided prostate biopsy [ 6 ]. Metastatic castration-resistant prostate cancer (mCRPC) represents the terminal stage of PC, characterized by the failure of antiandrogen therapy and distant metastases predominantly to the skeleton [ 7 ]. This condition is inevitably linked with a grim prognosis for the patient [ 8 ].…”