Grant: Foundation Grant

Cancer has become a major healthcare issue for Canada, and is now the leading cause of death in our country. 1 in 2 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 re-treat 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 program group in Hamilton, Ottawa and London 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 in the bone marrow space where they live. Furthermore, we have revealed that the bone marrow space itself changes to support leukemia, and is directly affected by chemotherapy. Available drugs can inhibit some changes in the bone, and our early findings indicate these drugs can reduce relapse when combined with chemotherapy. Our team of physicians, biochemists and stem cell biologists will define and test a series of new drugs that target proteins that inhibit surviving leukemic cells and change the bone marrow environment that will prevent relapse before it occurs, and activate normal blood stem cells to combat leukemia in patients in the next 7 years of support.