The enzyme PARP-1 is already well-known for its role in DNA damage repair, but scientists recently discovered that it also contributes to the growth and progression of androgen receptor-positive prostate cancer cells. This means that PARP inhibitors might be able to suppress androgen receptor activity, which fuels prostate tumor growth.
PARP-1, more formally known as poly(ADP-ribose) polymerase-1, is already a target of cancer therapy because of its involvement in DNA damage repair for cancer cells. In the latest research, a team led by Karen E. Knudsen, PhD, of Thomas Jefferson University in Philadelphia, Pennsylvania, learned through various in vitro and in vivo model systems that PARP-1 activity is required for androgen receptor function and is increased in castration-resistant prostate cancer. In this advanced stage of prostate cancer, chemotherapy and other treatments have little to no effect. Nearly 40% of men with prostate cancer progress to castration-resistant disease.
The investigators also found that inhibiting PARP-1 suppressed proliferation of cultured, primary human tumor specimens in a state-of-the art system.
“Collectively, these studies identify novel functions of PARP-1 in promoting disease progression, and ultimately suggest that the dual functions of PARP-1 can be targeted in human prostate cancer to suppress tumor growth and progression to castration-resistance,” wrote the authors in Cancer Discovery.