University of Houston researchers, led by assistant professor Daniel Frigo, have received two grants totaling $2.3 million from the National Institutes of Health’s National Cancer Institute to study two biochemical mechanisms, downstream of androgen receptors (AR), that are important in the pathogenesis of prostate cancer. Both studies, aiming for better disease detection and treatment, are being developed in collaboration with researchers at Baylor College of Medicine.
Androgens are hormones responsible for the development of male characteristics and for the normal growth and maintenance of the prostate. However, androgen activity through the androgen receptor (AR) is also responsible for the onset and progression of prostate cancer. Mutations in the AR, specifically when leading to decreased binding-specificity, might be involved in the progression of cancer and also in the eventual failure of AR blocking therapy in advanced stages of the disease. Activation of this receptor can also activate different genes that further stimulate cancer growth.
In a university news release, Dr. Frigo said of usual treatment procedures: “The standard of care for advanced prostate cancer is to block the AR molecule. One of the major ways to treat it is through androgen ablation therapy. You can either chemically castrate the patient to prevent him from making androgens, or you can administer a drug that blocks where androgens bind to the AR. But the AR is a sneaky molecule that can become reactivated in a number of different ways to get around these drugs.”
Due to AR’s evasive nature, treatments that might initially be successful can eventually fail. In light of this, the attributed grants will be used by Dr. Frigo’s team to investigate the poorly understood events that occur after AR signaling.
The first study will look into the metabolism of cancer cells, namely pathways involving the CaMKKbeta and AMPK proteins that allow cancer cells to use a wide range of nutrients for tumor progression: AR activates the CaMKKbeta gene, which in turn activates AMPK. Researchers are trying to validate this pathway as a new therapeutic target to eventually control and regulate cancer proliferation.
The second study will focus on Myc, an oncogene that regulates how cancer cells use the amino acid glutamine, which is indirectly involved in the control of harmful oncogenic species. Researchers believe that glutamine metabolism is important for tumor progression and are looking to target common pathways involving AR and Myc.
“We think there are elements of glutamine metabolism needed for cancer to progress, and we’re trying to identify one area that is common to both AR and Myc. Our aim is to find out what and where that is and, ultimately, target it,” Dr. Frigo explained. “Our long-term goal is to develop new metabolic-based therapeutic approaches for the detection and treatment of prostate cancer.”