A University of Houston (UH) research team is working to develop new prostate cancer therapies that target 5′-AMP-activated protein kinase (AMPK) as well as other metabolic pathway participants. Prostate cancer cells require chemical compounds called androgens for growth and survival. Androgen ablation therapies are a standard of care for late-stage prostate cancer, however, the majority of patients relapse within two years. Unfortunately, at this point in the disease’s progression, there are limited treatment options for the patient.
Daniel Frigo, an assistant professor with the UH Center for Nuclear Receptors and Cell Signaling (CNRCS) and his research group previously demonstrated that the androgen receptor (AR) regulates prostate cancer cell growth via AMPK, a regulator of cellular energy homeostasis. The group found that prostate cancer cells responded to androgen treatment by increasing rates of glycolysis as well as glucose and fatty acid oxidation, and this effect was dependent on androgen-mediated AMPK activity. The group also discovered that metabolic changes mediated by AMPK increased intracellular ATP levels and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-mediated mitochondrial biogenesis. This situation lends to distinct growth advantages for the prostate cancer cells. The Frigio group results taken together demonstrate that prostate cancer cell growth is enhanced by androgens co-opting the AMPK-PGC-1α signaling cascade. This was a significant finding because even though androgen therapies are no longer effective following relapse, androgen signaling is still active and its mechanism of action remains a potential therapeutic target. These data were published in Nature Oncogene November 2013.
Prostate cancer is the most commonly diagnosed malignancy among men in industrialized countries, with approximately one out of six American men being diagnosed. Close to a quarter of a million new cases of prostate cancer are expected this year. These numbers, and the data from Frigio’s research group emphasize the need to explore new and continue current studies that focus on metabolic-targeted therapies directed at AMPK and other metabolic pathways in order to develop the next generation of prostate cancer therapies.