From Lab to Clinic: 5 insights from The Journey of Discovering Lactate Transporter Inhibitors -written by Poonam Chanchlani (BCA, Data Science)

Scientists at the Giulio Superti-Furga Lab at CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, have introduced an innovative technique that enables the  identification of specific inhibitors associated with a lactate transporter linked to cancer and other medical conditions . The compound identified through this method could potentially serve as a new starting point for the development of cancer treatments. This groundbreaking study has been detailed in the journal Cell Chemical Biology.

 

Transporter proteins, particularly from the solute carrier (SLC) family, play a pivotal role in nutrient supply and removal within cells, affecting their metabolism and overall health. Despite their significance as potential therapeutic targets, many SLCs remain underexplored from a pharmacological perspective. The team led by Giulio Superti-Furga has devised a strategy to target lactate transporters SLC16A1 and SLC16A3, known to be associated with specific cancers and other diseases.

 

Lactate, a byproduct of glycolysis, functions not only as a metabolic waste but also as an energy source. Highly glycolytic cells secrete lactate, which neighboring cells utilize for energy, observed in tissues like skeletal muscle, brain, testes, and tumor microenvironments. Transport of lactate is facilitated by SLC16 family members, particularly SLC16A1 (MCT1) and SLC16A3 (MCT4). These transporters contribute to crucial processes such as immune suppression in tumors and treatment resistance.
 

Vojtech Dvorak, the study's lead author, explains the challenge of targeting SLCs due to functional redundancies among various transporters in cells. The team addressed this by identifying a synthetic lethality between SLC16A1 and SLC16A3, creating cell lines dependent on specific lactate transporters to find selective drugs.

 

The study unveils the Paralog-dependent isogenic cell assay (PARADISO) system and its use in developing a chemical probe, slCeMM1, that specifically targets SLC16A3. According to Superti-Furga, the lack of specific cell-based assays hinders drug target research, and the PARADISO system could extend its applicability beyond SLCs, aiding in the discovery of new therapeutic targets.