The Convergence of DNA Damage Checkpoint Pathways and Androgen Receptor Signaling in Prostate Cancer

摘要

It is increasingly clear that Castration Resistant Prostate Cancer is dependent on the Androgen Receptor. This has led to the use of anti-androgen therapies that reduce endogenous steroid hormone production as well as the use of androgen receptor antagonists. However, the androgen receptor does not act in isolation and integrates with a milieu of cell signaling proteins to affect cell biology. It is well established that cancer is a genetic disease resulting from the accumulation of mutations and chromosomal translocations that enables cancer cells to survive, proliferate, and disseminate. To maintain genomic integrity, there exists conserved checkpoint signaling pathways to facilitate cell cycle delay, DNA repair, and/or apoptosis in response to DNA damage. The androgen receptor interacts with, affects, and is affected by these DNA damage response proteins. This review will focus on the connections between checkpoint signaling and the androgen receptor in prostate cancer. We will describe what is known about how components of checkpoint signaling regulate androgen receptor activity and what questions still face the field.