Targeting metastatic castration-resistant prostate cancer: mechanisms of progression and novel early therapeutic approaches.
BACKGROUND
Advances in clinical research have led to official approval of several new treatments for metastatic prostate cancer in the last three years: sipuleucel-T, cabazitaxel, abiraterone acetate, radium-223 and enzalutamide. Although these agents have all been shown to improve overall survival in randomized Phase III trials, metastatic castration-resistant prostate cancer (mCRPC) remains incurable.


METHODS
First, the review summarizes the current literature on the biology of mCRPC. The emerging data are increasing our understanding of the mechanisms that underlie the pathogenesis of castrate resistance and where future treatment might be headed. In the second part of the review, the authors assess the future directions in disease therapy. Indeed, novel selected therapeutic approaches, including novel agents and combinatorial therapies, are showing promising early results.


CONCLUSIONS
Targeting different molecular pathways in combination with immunotherapy can be a promising direction in metastatic castration prostate cancer treatment. However, several challenges still exist including elucidating the optimal use and sequencing of these new agents. There are also challenges in both the design and the interpretation of the results from clinical trials.
University of Rome 'Tor Vergata', Tor Vergata Clinical Center, Department of Systems Medicine, Medical Oncology , V.le Oxford 81, 00133, Rome , Italy +390 620 908 190 ; +390 620 904 576 ; vittore.cereda@gmail.com.
Vittore
V
Cereda
Vincenzo
V
Formica
Gioia
G
Massimiani
Livia
L
Tosetto
Mario
M
Roselli
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*
D000970:Antineoplastic Agents