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Massey researchers awarded $1.5M to study combination therapy for triple negative breast cancer

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Joseph Landry, Ph.D., and David Gewirtz, Ph.D.

Scientists at VCU Massey Cancer Center were awarded $1.5 million from the U.S. Department of Defense to study whether a novel combination therapy can stimulate the immune system and enhance treatment response in triple negative breast cancer.

David Gewirtz, Ph.D., member of the Developmental Therapeutics research program at Massey, and Joseph Landry, Ph.D., member of the Cancer Molecular Genetics research program at Massey, received a three-year grant in 2019 to investigate how breast cancer cells are affected by a process called autophagy in hopes of identifying a more effective therapeutic strategy.

Autophagy is a cellular stress response process through which a cell will start to cannibalize itself in order to generate energy and compounds necessary to survive after chemotherapy or radiation treatment.

“It is a common mechanism that normal cells will use to survive in difficult environments, and is something that cancer cells will frequently exercise when they’re damaged by chemotherapies or radiation,” said Landry, an assistant professor in the Department of Human and Molecular Genetics at the VCU School of Medicine.

In some cases, autophagy has been shown to stimulate the immune response to detect and destroy cancer cells. Conversely, autophagy can also help cancer cells repair themselves and survive. Through this research, Gewirtz and Landry hope to identify a combination therapy for breast cancer that can steer autophagy further in the direction of its immune response function.

“Breast cancer is not highly immunogenic and therefore the involvement of the immune system might be minimal under normal therapeutic conditions, but if we can enhance an immune response, then we believe that we will improve sensitivity to therapy,” said Gewirtz, a professor in the Department of Pharmacology and Toxicology at the VCU School of Medicine.

Gewirtz and Landry are in the process of submitting research for publication that demonstrates that the chemotherapy drug doxorubicin (Adriamycin) damages DNA in triple negative breast cancer cells and promotes autophagy, meaning the cancer cells are able to survive the potential toxicity of the treatment. They also determined that if you inhibit NURF, the DNA-damaging effects of the chemotherapy are enhanced. NURF is a protein complex that regulates how the DNA is packaged and, as a result, how genes are expressed. This preliminary data serves as the basis for what they hope to achieve through their grant.

 “We’re trying to establish the proof of concept that inhibiting NURF in combination with chemotherapies will make difficult-to-treat breast cancers more treatable by stimulating the immune system,” Landry said. “Eventually, we hope to identify a drug that can be used in the clinic in combination with chemotherapies.”

In partnership with researchers from the University of Minnesota, the development of a NURF inhibitor drug is underway that has already shown tumor growth control in combination with doxorubicin. It is plausible that this research will hold clinical implications beyond the treatment of breast cancer.

Liliya Tyutyunyk-Massey, a former graduate student in the Department of Pharmacology and Toxicology at the VCU School of Medicine and currently a post-doctoral fellow at the National Institutes of Health, is closely involved with this research.

Written by: Blake Belden

Posted on: April 29, 2020

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