Adam Wolfe, MD, PhD, a radiation oncologist at the University of Arkansas for Medical Sciences (UAMS) 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 4-year ACS Clinician Science Development Grant will fund Dr. Wolfe’s study of KRAS and its connection to RAD18, a DNA repair enzyme also highly expressed in pancreatic cancer that prevents radiation from destroying the cancer cells.
“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 Dr. Wolfe, who is Assistant Professor in the UAMS Department of Radiation Oncology and has been studying pancreatic cancer since his residency at The Ohio State University. Dr. Wolfe has found that blocking the gene USP7 reduces RAD18 expression levels and increases cancer cell death following radiation.
Adam Wolfe, MD, PhD
The ACS grant will provide critical funding for Dr. 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 Dr. Wolfe. “In a second aim, we will test a novel USP7 inhibitor in a preclinical model of pancreatic cancer with radiation to determine if this combination strategy is effective and safe.”
A Growing Menace
According to the Centers for Disease Control, pancreatic cancer accounts for only 3% of new cancer diagnoses but has the highest mortality rate. It is the fourth-leading cause of cancer deaths in the United States for both men and women. Only 12% of patients live 5 years after being diagnosed. The American Cancer Society estimates 50,550 deaths from pancreatic cancer in 2023.
According to ASCO, pancreatic cancer diagnoses are rising overall, and the disease is expected to overtake colorectal cancer as the second-highest cause of cancer deaths in the United States. Dr. Wolfe attributes the increase to obesity and type 2 diabetes, which raise the risk of many cancers, including pancreatic.
