M.D./Ph.D. Student Receives Two Grants for Cancer Research

Randall J. Brenneman, Ph.D., an M.D./Ph.D. student pursuing a career in radiation oncology, has received two medical student grants to help support his research into the development of targeted cancer therapies.

Brenneman has been interested in radiation oncology since his undergraduate studies, when he majored in neuroscience at Franklin & Marshall College in Lancaster, Pennsylvania.

“It’s a challenging field, and when you have had family members affected by cancer, you want to join the fight,” he said. “Translational research to find new options for cancer therapy is very appealing to me, especially after seeing patients dying from this disease on the wards as a medical student.”

Brenneman has conducted research in the laboratories of Adrian S. Ishkanian, M.D., M.Sc., assistant professor of radiation oncology, and Eli Gilboa, Ph.D., professor of microbiology and immunology and Director of the Dodson Interdisciplinary Immunotherapy Institute, who was his dissertation advisor, and Alan Pollack, M.D., Ph.D., professor and Chairman of the Department of Radiation Oncology.

The first grant, $5,000 from the American Medical Association’s Seed Grant Research Program, takes effect this month and will fund exploration into identification of nuclease-resistant RNA aptamers that target irradiated human tumors.

“Previous work by the Gilboa laboratory has shown that small pieces of nucleic acid called aptamers can be used as a way to target cancer therapy to tumors,” said Brenneman. “Tumors make certain proteins that accumulate at high levels locally compared to the rest of the body. A collaborative effort between the Ishkanian and Gilboa laboratories has recently shown that radiotherapy can be used as a novel way to increase tumor expression of these proteins. The project will attempt to identify new aptamers that recognize proteins selectively increased in tumors after radiation therapy that can serve as tumor-targeting ligands for cancer therapy.”

The second grant, for which Brenneman was sponsored by Ishkanian and Pollack, is a Research Medical Student Grant from the Radiological Society of North America’s Research and Education Foundation that takes effect in June.

“This project will use radiotherapy-induced upregulation of tumor proteins as a new way to target an existing standard-of-care cancer treatment in the form of monoclonal antibodies,” said Brenneman. “They help fight cancer by directly killing tumor cells and have recently been used to improve the ability of a patient’s immune system to recognize and eliminate cancer cells.”

A challenge for monoclonal antibody therapy for cancer is that it can cause unwanted and dose-limiting side effects because they distribute throughout the body instead of localizing to tumors. Since radiation can induce preferential targeting of certain aptamers to irradiated tumors, a novel use of this phenomenon is to use the effect as a way to bring monoclonal antibodies directly to those tumors by connecting them to aptamers.

“This project, which is the result of substantial collaboration and support among the Ishkanian, Gilboa and Pollack laboratories, has the potential to substantially improve monoclonal antibody therapy for cancer through radiation-induced targeting to tumors,” said Brenneman.

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