The cyclin-dependent kinases pathway as a target for prostate cancer treatment: rationale and future perspectives.

• Treatment options for prostate cancer (PC) have greatly expanded in the last years. • Despite improvements in diagnosis and treatment options, PC remains one of the most frequent causes of mortality in men. • The cyclin-dependent kinases (CDK) pathway has a fundamental role for carcinogenesis. • CDK-inhibitors are novel agents representing a promising treatment approach in PC. • Several trials are evaluating the role of these agents in different stages of PC. The rapidly expanding scenario of treatment options for patients affected by prostate cancer (PC) is leading to improved outcomes; however, PC still represents one of the most frequent causes of male mortality. Thus, while translational research is trying to unravel the molecular landscape underlying carcinogenesis, disease progression and treatment resistance, several clinical trials are evaluating novel options to further expand therapeutic options. The cyclin-dependent kinases (CDK)-pathway represents a promising therapeutic target for different cancer types; due to the pivotal role of this pathway in the regulation of PC cell cycle, three CDK4/6-inhibitors (abemaciclib, palbociclib and ribociclib) are currently being investigated in several clinical trials. In this paper, we review the current knowledge on CDK-pathway and the mechanism of action of CDK-inhibitors; we discuss the biological rationale for their use in PC and the state of the art of clinical trials focused on the demonstration of their potential role in early or advanced stage, in hormone-sensitive and castration-resistant state. Finally, the potential application of precision oncology for treatment selection in PC is discussed. [ABSTRACT FROM AUTHOR]