The $1.1 million grant from the National Cancer Institute will be used to advance research into how certain molecules work to make cancer cells resistant to treatments that work initially by blocking the cancer-promoting action of the male hormone androgen. In advanced prostate cancers, even anti-androgen drugs can't prevent reactivation of the androgen receptor, leading to disease progression.
Investigators hope their findings provide insights into how prostate cancer becomes resistant to androgen withdrawal therapies and lead to more effective treatments for the disease.
The grant is one of 21 currently funded projects at the UC Davis Cancer Center tackling the problem of so-called "castration resistant" prostate cancer, which does not respond to withdrawal of male hormones. Prostate cancer is the most common cancer in American men, and is the second leading cause of cancer death in men. Median survival for men with castration-resistant prostate cancer that has spread to other parts of the body is one to two years.
The new grant, awarded to UC Davis Cancer Center director and urology professor Ralph deVere White, expands earlier research into the role of tiny strands of genetic material called microRNA in the progression of prostate cancer.
DeVere White and his team's preliminary research found that one specific microRNA — miR-125b — promoted prostate cancer cell growth midway through the disease process, making it fatal. The current research study will attempt to determine if the microRNA can be knocked out without interfering with other essential molecular functions, suggesting that it could be a good target for potential therapy.
The research team earlier demonstrated that MiR-125b was present at high levels in prostate cancer cells that were castration-resistant, also known as androgen-independent. However, they also found high levels in androgen-dependent cells, suggesting that the microRNA is involved in the prostate cancer process even prior to androgen withdrawal. More recently, they found that miR-125B directly targets three genes that suppress tumor growth — P53, BAK1 and PUMA, work that will soon be published in the journal The Prostate.
The new round of funding will allow deVere White and project scientist Xu-Bao Shi to test their hypothesis that miR-125b promotes castrate resistance by repressing the function of genes such as P53 that suppress that growth.
"This is a novel hypothesis," said deVere White. "If we can understand the functions of miR-125b in prostate cancer, and determine whether it can be used as a potential biomarker or drug target for the disease, we can make tremendous progress against this devastating disease."
UC Davis Cancer Center is the only National Cancer Institute-designated center serving the Central Valley and inland Northern California, a region of more than 6 million people. Its top specialists provide compassionate, comprehensive care for more than 9,000 adults and children every year, and offer patients access to more than 150 clinical trials at any given time. Its innovative research program includes more than 280 scientists at UC Davis and Lawrence Livermore National Laboratory. The unique partnership, the first between a major cancer center and national laboratory, has resulted in the discovery of new tools to diagnose and treat cancer. Through the Cancer Care Network, UC Davis is collaborating with a number of hospitals and clinical centers throughout the Central Valley and Northern California regions to offer the latest cancer-care services.