Adam Wolfe, MD, PhD, a radiation oncologist at the University of Arkansas for Medical Sciences Winthrop P. Rockefeller Cancer Institute has received a $583,200 grant from the American Cancer Society (ACS) to study radiation resistance in pancreatic cancer, a lethal disease with the highest mortality rate of all cancers.
The four-year ACS Clinician Science Development Grant will fund Wolfe’s study of KRAS, a mutated gene that is present.
in 90% of all pancreatic cancer cases, and its connection to RAD18, a DNA repair enzyme also highly expressed in pancreatic cancer that prevents radiation from destroying the cancer cells.
In most cancers, radiation, along with chemotherapy, destroys cancer cells that have developed from damaged DNA.
“In pancreatic cancer, these therapies are challenging due to the presence of intrinsic resistance mechanisms from heightened DNA repair — a consequence of the mutated oncogene KRAS,” said Wolfe, an assistant professor in the UAMS Department of Radiation Oncology who has been studying pancreatic cancer since his residency at Ohio State University.
Wolfe has found that blocking the gene USP7 reduces RAD18 expression levels and increases cancer cell death following radiation.
The ACS grant will provide critical funding for Wolfe’s lab at the UAMS Winthrop P. Rockefeller Cancer Institute, where he will continue to study the KRAS-RAD18-USP7 pathway.
“By understanding this cancer-related pathway, we can start to design targeted therapies to inhibit the increased DNA repair after radiation,” said Wolfe.
“In a second aim, we will test a novel USP7 inhibitor in a pre-clinical model of pancreatic cancer with radiation to determine if this combination strategy is effective and safe.”