MCI researchers publish novel findings that could improve management of prostate cancer
The study unveils a novel mechanism to explain contradictory actions of androgens in prostate cancer, offering promising potential in managing prostate cancer more effectively.
By Lindsay Hughes
Srijan Acharya, Ph.D., a postdoctoral researcher at the USA Health Mitchell Cancer Institute, serves as the lead author on a research study that offers promising potential in managing prostate cancer more effectively.
His research, titled, “Biphasic transcriptional and post-transcriptional regulation of MYB by androgen signaling mediates its growth control in prostate cancer,” unveils a novel mechanism to explain contradictory actions of androgens in prostate cancer. He conducted his research in the lab of Ajay Singh, Ph.D., professor of pathology at the Frederick P. Whiddon College of Medicine at the University of South Alabama. The work was supported by funding from the National Cancer Institute and the Mitchell Cancer Institute.
Androgens, which are a group of male hormones, play a significant role in the growth of prostate cancer. “Therefore, lowering their levels or inhibiting their function remain frontline treatment options for patients with advanced or metastatic prostate cancer,” Singh said.
Although androgen-suppression therapy – also known as hormone therapy – is effective in most patients, it inevitably fails in the long term. “Interestingly, it has been observed that androgens at high doses can also suppress prostate cancer growth, which has led oncologists to examine androgen supplementation as a therapeutic approach in clinical trials,” Singh said. “The resulting data is promising; however, the mechanisms underlying the dichotomous action of the androgens remain unclear, which could yield molecular signatures to help in prospective identification of likely responders.”
Their research successfully identified that androgens confer their growth-promoting action by inducing the expression of a protein, MYB, which the group identified earlier to be overexpressed in prostate cancer. “Interestingly, we found that at high doses androgens suppressed the expression of MYB through induction of negative regulatory microRNA, miR-150,” Acharya said.
“Thus, we have identified MYB and miR-150 as two important functional targets downstream of androgen signaling, whose levels can be used for therapeutic planning and to monitor the response of androgen-targeted therapies in prostate cancer,” Singh added. “In addition, newer therapeutic approaches that either inhibit MYB function or enhance miR-150 levels in prostate cancer cells can be evaluated to manage prostate cancer more effectively.”
Other members of the research team responsible for the findings include Shashi Anand, Ph.D., a postdoctoral fellow in pathology; Mohammad Aslam Khan, Ph.D., a senior research associate at the Mitchell Cancer Institute; Haseeb Zubair, Ph.D., a postdoctoral fellow in pathology; Sanjeev Srivastava, Ph.D., formerly a researcher at the MCI and currently an analytical scientist at Johnson & Johnson; and Seema Singh, Ph.D., professor of pathology at the Whiddon College of Medicine.