TITLE:
New Molecular Targets in Metastatic Prostate Cancer
AUTHORS:
Francesco Pantano, Giulia Ribelli, Michele Iuliani, Marco Fioramonti, Mark Leakos, Alice Zoccoli, Daniele Santini, Giovanni Muto, Giuseppe Tonini
KEYWORDS:
Prostate Cancer, Target Therapy
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.7 No.6,
June
17,
2016
ABSTRACT: Prostate
cancer (PCa) is the second leading cause of cancer death in men. Despite
initial responses, almost all patients progress to castration-resistant
prostate cancer (CRPC). Over the past decade, increased understanding of the
mechanisms that drive resistance to castration has led to the development of
next-generation androgen receptor targeting agents such as abiraterone acetate
and enzalutamide. Moreover in the last few years, results from large Phase III
trials led to the approval of an α-emitter
(radium-223), the bone resorption-targeting drug denosumab and an immunotherapy
(sipuleucel-T) that showed improvements in terms of overall survival. In the
field of metastatic CRPC, other novel therapeutics have recently been proven to
extend survival via distinct mechanisms of action such as the new and more
potent classes of androgen inhibitors, ortonel, ARN-509 and galeterone, the
endothelin A receptor antagonist zibotentan, the Src inhibitor dasatinib, the
c-MET inhibitor cabozantinib and the immune checkpoint inhibitor ipilimumab. This
review aims to revisit the evolution of androgen receptor targeting
therapeutics and to discuss other important alternative biologic pathways that
have given rise to new agents in metastatic prostate cancer.