Grant: Project Grant

Cancer has become a major healthcare issue for Canada, and is now the leading cause of death in our country. Two in 5 Canadians may be afflicted with cancer, and 1 in 4 Canadians are expected to die from it. Although progress in therapy has been made in many cancers, such as breast and prostate, treatment options for other cancers remain stagnant. This is exemplified by Acute Myeloid Leukemia (AML), a type of blood cancer where dysfunctional leukemic cells take over the blood system. Disease burden can initially be reduced by lowering the leukemic cell numbers (called Remission) with chemotherapy, but the disease usually comes back within 2 years (called Relapse). When AML relapses, the option is to retreat the cancer with the same chemotherapy but at a higher dose, and for longer. Unfortunately, the disease usually becomes resistant to treatment and can no longer be controlled. However, the exact reason for AML relapse and resistance to chemotherapy remains unclear. Our lab has now identified rare leukemic cells that: a) survive chemotherapy and b) regrow to give rise to relapsed disease. Detailed tests on these unique cells revealed that before they regenerate AML disease, they begin to express leukemia-specific proteins that give them a growth advantage. Available drugs can inhibit some of these proteins, and our early findings indicate these drugs can prevent relapse when combined with chemotherapy without harming the normal blood system. Our proposal takes advantage of our identification of human AML cells that cause relapse, and will examine how leukemic disease evolves and why it becomes resistant to chemotherapy. We will test a series of new drugs that inhibit each of a set of proteins turned on by surviving leukemic cells, to prevent relapse before it occurs. Our goal is to apply the knowledge we gain from this work towards clinical trials for AML, using the best drug combinations we find over the next 5 years.