Grant: Operating Grant - Priority Announcement: Breast Cancer

Nine out of ten Canadians killed by cancer, die because their tumour has spread to other parts of their body. The spread of cancer occurs when tumour cells escape the original primary tumour and colonize other organs to form life-threatening tumour metastases. Thousands of tumour cells can escape a primary tumour every day, but most of these do not grow into metastases. We are beginning to realize that normal cells in the body can help tumour cells to survive and grow into metastases. If we can understand how normal cells encourage the development of tumour metastases, we will be able to design more effective therapies to treat metastatic cancer. Most primary tumours contain cells that are poorly oxygenated (hypoxic) compared to cells found in normal tissues. We have discovered that these hypoxic tumour cells produce proteins that cause normal cells to be released from the bone marrow and to build-up in tissues such as the lung and liver. These bone marrow cells create nests for metastasizing tumour cells to inhabit, providing fertile regions of tissue that allow tumour cells to grow into large tumour metastases. We predict that therapies to prevent bone marrow cells from building up in tissues will be effective for treating metastatic cancer. My research team will study the proteins that cause bone marrow cells to build-up in the lungs and liver. We will determine how surgical tumour removal and chemotherapy treatments change bone marrow cell numbers in tissues. We will also test new therapies to prevent the build-up of bone marrow cells in tissues. Our studies will provide insight into how hypoxic tumour cells and normal cells contribute to the spread of cancer. To improve the health of Canadians, we need to better understand the leading cause of cancer-related deaths. This proposal will help us to understand how primary tumours corrupt normal cells to increase the spread of cancer, and will enable the design of improved treatments for patients with metastases.