Cancer treatments with targeted
therapy have gained immense interest due to their low levels of toxicity and high selectivity.
Proteolysis-Targeting Chimeras (
PROTACs) have drawn special attention in the development of
cancer therapeutics owing to their unique mechanism of action, their ability to target undruggable
proteins, and their focused target engagement.
PROTACs selectively degrade the target
protein through the
ubiquitin-
proteasome system, which describes a different mode of action compared to conventional small-molecule inhibitors or even
antibodies. Among different
cancer types,
prostate cancer (PC) is the most prevalent non-cutaneous
cancer in men. Genetic alterations and the overexpression of several genes, such as FOXA1, AR, PTEN, RB1, TP53, etc., suppress the immune response, resulting in drug resistance to conventional drugs in
prostate cancer. Since the progression of ARV-110 (
PROTAC for PC) into clinical phases, the focus of research has quickly shifted to
protein degraders targeting
prostate cancer. The present review highlights an overview of
PROTACs in
prostate cancer and their superiority over conventional inhibitors. We also delve into the underlying pathophysiology of the disease and explain the structural design and linkerology strategies for
PROTAC molecules. Additionally, we touch on the various targets for
PROTAC in
prostate cancer, including the
androgen receptor (AR) and other critical
oncoproteins, and discuss the future prospects and challenges in this field.