Although recent advances in the treatment of castration-resistant prostate cancer (CRPC) have significantly improved patient outcomes, advanced prostate cancer is still associated with substantial morbidity and mortality, particularly in patients who develop resistance after multiple lines of therapy. Various cell signaling, DNA repair, and epigenetic enzymatic pathways are being targeted with small-molecule inhibitors in order to identify treatment strategies for patients with CRPC. In this review, we discuss novel targets and agents, studied preclinically and now being validated in clinical trials, including poly ADP-ribose polymerase (PARP), enhancer of zeste homologue 2 (EZH2), hedgehog pathway, MDM2/p53, and tyrosine kinase inhibitors. Further, we outline current approaches for novel prostate cancer vaccines such as DCVAC/PCa, PROSTVAC-V/F, MVI-816, CV9104, and PF-06753512. This wide spectrum of potential treatment strategies holds promise for additional improvements in the treatment of patients with CRPC, as these novel agents are aimed at targets known to be associated with growth and malignant progression of prostate cancer. If primary study endpoints are met, findings from ongoing phase III trials of well-tolerated and active combinations may provide new effective treatment options for advanced prostate cancer and thereby contribute to enhanced disease control in CRPC patients.
Cancer treatment reviews. 2019 Mar 19 [Epub ahead of print]
Fred Saad, Neal Shore, Tian Zhang, Shikhar Sharma, Helen K Cho, Ira A Jacobs
Centre Hospitalier de l'Université de Montréal/CRCHUM, Montréal, Quebec, Canada. Electronic address: ., Carolina Urologic Research Center, Myrtle Beach, SC, USA., Duke Cancer Institute, Durham, NC, USA., Pfizer, San Diego, CA, USA., Pfizer, New York, NY, USA.