Although effective at killing cancer cells, most chemotherapy agents are also toxic to healthy cells. The discovery of new drugs that have better cancer cell-specific toxicity could reduce side effects and improve quality of life for cancer patients.
A unique property of many cancer cells is their altered metabolism of glucose. Specifically, cancer cells consume and metabolise excess glucose (above that required for ATP generation) for the synthesis of nucleotides, proteins, and lipids, and export lactate into the extracellular environment. This type of metabolism, termed aerobic glycolysis or the ‘Warburg effect’, facilitates tumour growth and metastasis. However, this unique characteristic of cancer cells exposes a potential weakness that can be exploited for therapy.
We therefore performed a phenotypic drug screen of more than 5000 small molecules to identify those that altered the Warburg effect. From this screen, we identified our lead compound called BAM10. BAM10 reduces glycolysis and glucose uptake, while simulaneously increasing glucose oxidation. Importantly, BAM10 is selectively toxic to a broad range of cancer cells in vitro and has synergistic anti-cancer properties with vitamin C in vivo. Therefore BAM10 represents an attractive drug candidate for cancer therapy that may be used in combination with vitamin C with little or no toxicity to healthy tissues.