Most cancer cells are highly glycolytic, metabolizing glucose to lactic acid even when sufficient oxygen is available to perform oxidative metabolism, a phenomenon known as the Warburg effect. The Warburg effect has been shown to promote tumor growth, enable survival, and stimulate metastasis. In this project, we describe a strategy to directly antagonize the Warburg effect in cancer cells through the inhibition of MCT4, a lactic acid exporter that is required for the Warburg effect and is highly upregulated in many cancer indications. We have discovered a potent and selective small molecule inhibitor of MCT4. In this project, we will use this compound to validate MCT4 as a cancer target, using both in vitro and in vivo approaches. We will also develop more potent MCT4 inhibitors with the ultimate goal of evaluating MCT4 inhibition in clinical trials. 1
Cancer is the leading cause of death in the developed world. A promising strategy for anti-cancer therapy is to target aberrant metabolic pathways in cancer cells. In this project, we propose to target the metabolic factor MCT4, a lactate transporter that is highly upregulated and plays a important role in cancer indications that include renal cell carcinoma, a common type of kidney cancer with around 50,000 US diagnoses each year, and with few therapeutic options. In this manner, Vettore hopes to address the considerable unmet need for potent and novel anti-cancer therapies.