Ongoing research by a Vanderbilt-Ingram Cancer Center scientist into how cells transform into abnormal versions of themselves that are the precursors to stomach cancer has received support from the American Association for Cancer Research (AACR).
Eunyoung Choi, PhD, associate professor of Surgery, is one of three inaugural recipients of an AACR-Debbie’s Dream Foundation Innovation and Discovery Grant.
The AACR and the Debbie’s Dream Foundation: Curing Stomach Cancer, which was founded by Debbie Zelman, established the award to encourage innovation and translation of ideas from basic research into new treatment options for gastric cancer. Zelman — an attorney, mother of three young children, and a wife — was diagnosed at age 40 with stage IV stomach cancer in 2008 and started the foundation a year later. After nearly a decade of advocacy on behalf of stomach cancer patients, their families, and caregivers worldwide, she died on Dec. 23, 2017.
“I’m truly honored to receive the 2023 AACR-Debbie’s Dream Foundation Innovation and Discovery Grant,” Choi said. “This grant will allow me to conduct a high-risk project for a novel drug target as a prevention and early intervention strategy for gastric cancer and to obtain key data for future funding.”
Choi said she remains appreciative of a 2017 Career Development Award for $200,000 from Debbie’s Dream Foundation that was one of her first funding grants as an independent investigator.
Recent research led by Choi revealed how metabolic changes spurred by fatty acids contribute to the transformation of cells into abnormal versions of themselves that are the precursors to stomach cancer.
The study, published Jan. 23 in Gastroenterology, showed that oncogenic metabolic rewiring is an essential adaptation for the high energy demand of abnormal, dysplastic cells. In a mouse model, the researchers introduced the KRAS oncogene in gastric chief cells to drive a sequential carcinogenic cascade of gastric cancer and identified the metabolic reprogramming that leads to dysplastic progression by turning on altered fatty acid metabolism.
The altered fatty acid metabolism produces a long chain fatty acid, called Eicosenoic acid, through SCD (a stearoyl-CoA desaturase) and fuels the hyperproliferation of dysplastic cells. The researchers concluded that KRAS expression drives the full spectrum of gastric carcinogenesis and that metabolic rewiring involving the fatty acid desaturation is essential for the high energy demands of dysplastic cells and carcinogenic transition of precancerous metaplasia.
In this next step supported by the $50,000 grant, Choi and her research team seek to evaluate the potential of aberrant fatty acid metabolism as a novel druggable target for prevention or treatment of gastric cancer.