National Cancer Institute Awards RFU Researcher Grant to Crack the Epigenetic Code of Pancreatic Cancer Muscle Wasting

Paige Arneson-Wissink, PhD, assistant professor of biochemistry and molecular biology in the Center for Genetic Diseases, has been awarded a three-year, $747,000 grant from the National Cancer Institute (NCI) to support her research on cachexia in pancreatic ductal adenocarcinoma (PDAC), an aggressive and highly lethal form of cancer.

Cachexia, a metabolic disorder that causes the body to break down its own muscle and fat — regardless of food intake — accounts for 20%–25% of all cancer-related deaths. It contributes to functional impairment, limits eligibility for anti-tumor therapies, and significantly reduces quality of life. Nutritional supplementation alone is insufficient to prevent tissue loss, and effective targeted therapies are limited.

“Our project is innovative in its use of advanced epigenetic techniques combined with a novel preclinical model of PDAC survivorship,” Dr. Arneson-Wissink said. “Together, these tools allow us to define the epigenetic reprogramming events that persist after tumor clearance and increase vulnerability of muscle to nutritional stress.”

PDAC accounts for approximately 90% of pancreatic cancer cases. Its incidence is relatively low but rising. Globally, an estimated 495,000–510,000 new cases are diagnosed each year, including approximately 64,000–66,000 in the United States. Pancreatic cancer is projected to become the second leading cause of cancer-related death in the U.S. within the next decade. It occurs predominantly in individuals aged 65 and older.

Dr. Arneson-Wissink’s recent findings demonstrate that systemic inflammation in PDAC impairs the liver’s ability to adapt to ketogenic metabolism during periods of nutritional stress, contributing to muscle wasting. Inhibition of hepatic STAT3, a key liver signaling protein, restores ketogenic capacity and prevents muscle loss in PDAC preclinical studies. These findings provide the first evidence that enhancing hepatic fatty acid oxidation prevents cachexia progression.

“We are pleased to see Dr. Arneson-Wissink’s work recognized by the NCI,” said Janice Urban, PhD, RFU Interim Executive Vice President for Research. “Her research aims to improve the quality of life from diagnosis through survivorship by advancing our understanding of the metabolic interactions that drive cancer-associated cachexia.”