Grant: Operating Grant

Increasing evidence reveals that cancer has altered metabolism. The result of this change is an increase in metabolic byproducts, which in turn are responsible for signals that are unique in cancer cells. Identification and targeting the distinctiveness in cancer cells provides an opportunity to find novel targets and develop drugs that are selective for cancer cells and have negligible side effects for healthy cells. The focus of this project is to investigate the changes in the energy generating systems of tumour cells. The by-products of energy generation are breakdown of oxygen known as reactive oxygen molecules. These reactive oxygen molecules lead to abnormal signaling and may be associated with the cancer cell properties, such as uncontrolled growth and metastasis. We discovered in the energy producing sites of cancer cells a major protein source responsible for generating an abnormally high level of reactive oxygen molecules, called GPD2. We used sophisticated tools to identify inhibitors of this protein. Here we propose to further refine our inhibitor selection process and examine their biological consequences for cancer cells. This source of reactive oxygen molecules will be crystallized and its structure will be resolved. We will conduct sophisticated structure alterations and the potential mechanism(s) by which the inhibitors could block the production of reactive oxygen molecules will be determined. Limiting the ability of tumours to generate reactive oxygen molecules will reduce their ability to grow. This novel strategy would provide a new class of anticancer agents that target the energy producing sites of cancer cells and halt the abnormal processes in these cells.