Mohammad Saleem Bhat - Hormel Institute

Department of Defense honors Dr. Saleem’s cutting-edge prostate cancer research

Promising research at The Hormel Institute focused on effectively attacking a form of prostate cancer resistant to chemotherapy is being recognized nationally by the U.S. Department of Defense.

Dr. Mohammad Saleem, leader of the Molecular Chemoprevention and Therapeutics research section at The Hormel Institute, University of Minnesota had work recently featured as one of three prostate cancer research projects included in the Department of Defense’s “2014 Research Highlights” section.

Saleem, an assistant professor who brought his research to The Hormel Institute four years ago from the University of Wisconsin, is the recipient of a New Investigator Award from the Department of Defense Prostate Cancer Research Program. Saleem and his team have provided compelling evidence that a gene known as BMI1 plays a crucial role in determining the fate of tumors treated with chemotherapy.

“I am greatly honored and encouraged to know that the Department of Defense views my research as a potential key to overcoming the molecular barrier for treating aggressive prostate cancer in men,” Saleem said.

Castration-resistant prostate cancer (CRPC) is a deadly form of prostate cancer that is difficult to treat, and little is known about the reasons contributing to it, according to the DOD. Given that, identifying one or more critical molecules involved in conferring chemoresistance would be a significant advancement in developing new ways to prevent or treat that form of prostate cancer.

Recent advancements in cancer genomics have paved a way to understanding the causes and mechanisms underlying chemoresistance and the survival of prostate tumor cells during and after chemotherapy, the DOD says. Recent reports indicate involvement of several genes, including a group known as the Polycomb gene repressor family, which has been associated with several types of cancer, including prostate cancer. The emergence of BMI1 – a specific member of the Polycomb family – as a gene involved in cancer stem-cell renewal makes it an attractive target for further investigation.

Saleem and his researchers have identified a unique mechanism through which BMI1 rescues tumor cells from chemotherapy by regulating the activity and binding of the TCF4 transcription factor to the control region of BCL2, an anti-apoptotic gene. They also noticed that BMI1 is capable of driving normal cells to an over-active growth state by breaking their normal process of aging and death, suggesting that BMI1 possibly plays a vital role in breaking the sleeping mode of tumor cells and driving them toward a rapid increase in numbers.

“The fact that BMI1 expression is not influenced by androgen, which is the target of most chemotherapy treatments, further suggests that BMI1 might play a role in driving indolent disease to a more aggressive, androgen-independent disease state,” according to the DOD report on Saleem’s research.

Work by Saleem’s section also tested the ability of BMI1 blockade to enhance the results of docetaxel treatment, a commonly used therapy that can lower PSA levels in prostate-cancer patients by more than 50 percent but is not able to completely eliminate the tumor. Researchers at The Hormel Institute showed that targeting BMI1 in chemoresistant cells sensitizes them to docetaxel therapy, and that the success of docetaxel therapy is highly dependent on the BMI1 level.

“This suggests that targeting BMI1 should be part of a therapeutic strategy to combat chemoresistant cancer, and BMI1-specific interventions may provide opportunities to enhance the efficacy of chemotherapy in a large group of prostate cancer patients,” the DOD says.

The Hormel Institute, University of Minnesota, is a world-renowned medical research center in Austin, Minn., focused on discoveries leading to the prevention and control of cancer. In July 2014, The Hormel Institute will undergo a major expansion that will about double the size of its state-of-the-art facility, adding 20 laboratories and needed space for its International Center of Research Technology. The Hormel Foundation is providing a $13.5 million match to the State of Minnesota’s bonding funding for the expansion. The Hormel Foundation is committing an additional $9.5 million to recruit top scientists, equip labs with state-of-the-art technologies, and create a cutting-edge environment for progressive cancer research.

 

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