Grant: Project Grant

Late-stage, therapy-resistant cancers remain difficult to treat and urgently requires better therapeutics. A common feature of advanced cancers is the altered processing of glucose (sugar) as an energy source. In contrast to normal cells, many cancer cells use glucose to substantially increase lactic acid secretion into the surrounding environment. This extra lactic acid supports cancer growth in many important ways. Most vitally, it can help cancer cells avoid destruction by the patient's immune system. One critical protein involved in this process is MCT4, which transports lactic acid out of cells. We have previously shown that advanced prostate cancer (PCa) is one type of cancer that exhibits this altered metabolism. Blocking lactic acid secretion by reducing MCT4 levels can stop advanced PCa cells from growing. It can also restore the immune system's abilities to destroy cancer cells. We recently used a special, computer-based, state-of-the-art drug discovery platform (one of the few available in Canada) to quickly develop a new class of anti-MCT4 drugs. Here, we propose to further improve these MCT4 inhibitors. Additionally, we have a unique panel of lab-grown tumours taken from real patients with advanced cancers. Experiments using these tumours can accurately predict patient response to therapy and can show us whether the improved MCT4 drugs are effective at stopping advanced cancer growth. By 1) targeting a fundamental aspect of cancer biology, 2) using a unique computational approach, and 3) accurately predicting patient response, we will be able to successfully develop an effective anticancer drug. Funding this project will accelerate the development of a new MCT4-targeting therapeutic useful for clinical trials in patients with advanced cancers. Given the fact that this method of utilizing sugar is widespread among many aggressive cancers, the successful completion of this project will broadly improve therapy for a wide range of cancer patients.