DALLAS – July 31, 2024 – Researchers at UT Southwestern Medical Center have discovered that a diet free of the amino acid tryptophan can effectively halt the growth of liver cancer in mice. Their findings, published in Nature Communications, offer new insights for dietary-based cancer treatments and highlight the critical role of the tryptophan metabolite indole 3-pyruvate (I3P) in liver tumor development.
“This work demonstrates that tailored dietary modulation may serve as a powerful adjuvant in cancer treatment,” said study leader Maralice Conacci-Sorrell, Ph.D., Associate Professor of Cell Biology and Children’s Medical Center Research Institute at UT Southwestern (CRI) and a member of the Cellular Networks in Cancer Research Program of the Harold C. Simmons Comprehensive Cancer Center. “It builds on our lab’s discovery that the universal oncogene MYC increases the demand for tryptophan in liver tumors.”
Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related mortality worldwide, according to 2020 data from the World Health Organization, with limited options for effective treatment and a five-year survival rate of about 30%. The study shows that growth of liver cancers driven by the MYC oncogene is particularly dependent on tryptophan, which is converted into I3P as well as other metabolites.
By removing tryptophan from the diet of mice, researchers stopped the growth of MYC-driven liver tumors and restored normal gene expression in liver cells. Notably, this dietary intervention did not affect protein synthesis in normal cells, suggesting a targeted therapeutic approach that spares healthy tissues.
“Liver tumors require large amounts of tryptophan to generate the oncometabolite I3P,” Dr. Conacci-Sorrell said. “A tryptophan-free diet prevents liver tumor growth by a mechanism that depends on I3P but is independent of translation, the process by which proteins are synthesized from amino acid building blocks. Because tryptophan is the amino acid with the lowest abundance in the proteome, short-term dietary manipulation is safe for healthy tissues but not for cancer cells.”