Grant: Project Grant

In all cancer cells, a series of fundamental metabolic changes occur that enable growth and spread of tumours throughout the body. Hence, these metabolic changes are important potential therapeutic targets in the treatment of cancer. An important metabolic change that occurs, called the Warburg effect, is related to how cancer cells generate cellular energy to feed their growth and survival. A consequence of the Warburg effect is accumulation of damaging intracellular acid, and cancer cells must have systems in place to counter acid accumulation. The only known system involves turning on acid pumps to pump the acid out of the cell into the surrounding tumour environment, and drugs are currently being developed against this limited set of targets. Using a discovery-based approach we have identified over thirty new potential targets of acid stress in cancer cells. The objective of this grant proposal is to validate roles for these targets in growth and survival of cancer cells and to test them as potential therapeutic targets using animal tumour models. Identifying additional systems that cancer cells use to survive acid stress will provide insight and facilitate novel approaches in the treatment of cancer, and will potentially lead to development of new classes of anti-cancer drugs.