In a study funded by FCF, scientists at Cornell University analyzed the differences in the proteins and metabolites present in fibrolamellar carcinoma (FLC) and normal tissues to better understand the metabolism of the disease. Their findings, published in Cell Reports Medicine on August 28, offer deep insights into the metabolic alterations that occur in FLC, potentially paving the way for the development of targeted therapies.

The study was led by Donald Long Jr., Howard Hughes Medical Institute Gilliam Fellow, and Praveen Sethupathy, professor of physiological genomics and Chair of the Department of Biomedical Sciences at Cornell. Key findings of the study include:

• Profiling and functional studies show a lack of dependence of FLC on glycolysis, a metabolic pathway that converts glucose into pyruvate.
• Instead, metabolic analyses and tumor slice tests show a reliance on the amino acids glutamine and serine for pyruvate production.
• In addition, FLC cells may be highly dependent on serine dehydratase (SDS), an enzyme that converts serine to pyruvate and ammonia, to sustain tumor viability.
• Furthermore, the production of proline, a molecule needed to build the fibrous bands that are characteristic of this cancer, is increased due to high activity of a specific enzyme (ornithine aminotransferase) and low activity of another enzyme (ornithine transcarbamylase).
• FLC may also rely heavily on the voltage-dependent anion channel (VDAC), a key protein in mitochondria that controls the flow of molecules like pyruvate.

According to Praveen Sethupathy, “Our findings point to specific features of the cancer that represent therapeutic vulnerabilities, and could be very useful for testing specific drug combinations.”

Click here to read and download the published study.

A brief “plain English” summary of the article is available here. In addition, the Cornell Chronicle, a site that publishes daily news about research, outreach, events and the Cornell community, recently published the following article about the study – “Rare, deadly liver cancer rewires cell metabolism to grow“.