Timeframe: 2025 – 2027
Goal: Determine if targeting SLC16A14 could be a useful treatment approach for FLC.
Principal Investigator: Sean Ronnekleiv-Kelly, MD
Study overview: Recently, Dr. Ronnekleiv-Kelly used sophisticated genetic engineering to create a highly promising mouse model of FLC and other cancers driven by the DNAJB1-PRKACA (DP) gene fusion. Dr. Ronnekleiv-Kelly’s first goal in this new study will be to characterize the progression of DP-driven cancers in the new model. This will help pinpoint the direct actions of the DP oncogene that are most critical to the development of FLC. In turn, these studies may uncover potential targets for new therapies.
The project’s second aim is to utilize the mouse model to determine the function of a specific gene, SLC16A14 (also known as MCT14), that has previously been identified as playing a critical role in FLC. Studies in Praveen Sethupathy’s lab at Cornell University revealed that this gene is highly expressed in FLC cells, at levels far above the expression in other human cancers.
SLC16A14 is a member of a transporter family of proteins that shuttle specific metabolites in and out of cells across the cell membrane, or across the membranes of organelles such as mitochondria, the “energy powerhouses” of the cell. Some SLC16 family members transport simple molecules such as glucose or related sugars or amino acids. However, the metabolites transported by the SLC16A14 protein have not yet been identified.
This study aims to determine how SLC16A14 is linked to the metabolic changes and survival of FLC cancer cells. Determining the exact function of this protein will help determine if an inhibitor of SLC16A14 could be a valuable therapeutic for FLC.