All advanced stage tumors adopt vigorous glycolysis and the production of lactic acid to produce energy and other essential metabolites for proliferation. Export of this lactic acid out of the cell is essential to prevent a decrease in intracellular pH and avoid apoptosis.  Lactic acid influx and efflux from cells is facilitated by members of the mono-carboxylate transporter family known as MCT1 and MCT4. Thus, our hypothesis is that target inhibition of MCT1 and MCT4 with specific, novel, small molecule inhibitors will lead to vulnerability and death of cancer cells within both hypoxic and aerobic regions of neoplastic tissue. Over the past three years we have created novel small molecule MCT inhibitors and synthesized and evaluated several new compounds.  From these studies, we have discovered numerous potent MCT inhibitors that are active at very low nM concentrations. Anticancer efficacy studies in nude mice using a colon cancer model and preliminary toxicology studies in healthy mice have proven that these new molecules efficiently reduced the tumor growth without causing any systemic toxicity. MCT inhibitors have the potential to act as single agent anti-cancer agents as well as in combination with standard chemo/radiotherapy to realize their synergistic potential.

Novel small molecule MCT inhibitors as anticancer agents

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.