Grant: Operating Grant - PA: Cancer Research (bridge funding)

The white blood cells circulating in our blood stream represent the frontline defense of the immune system against infection. The successful and accurate targeting of white blood cells to inflamed or damaged tissues is facilitated by cell adhesion receptor proteins, termed integrins, which are expressed on the surface of these cells. These integrins facilitate white blood cell attachment to the blood vessel wall, thus enabling their accumulation at the affected tissue. The same attachment mediated by integrins also promotes the ability of the white blood cells to survive and grow. Unwanted accumulation of white blood cells also impact upon progression of blood cancers that include leukemia and lymphoma. In blood cancers, the adhesion or accumulation of cancerous blood cells allow the tumour to spread body wide and hinder effective treatment. Furthermore, studies have now revealed that the attachment via integrins lead to chemotherapeutic drug resistance acquired by the tumour cells. This is believed to be the major contributing factor for tumour relapse following chemotherapy. So while tumour cells circulating freely in the blood stream are easily killed, those attached in the bone marrow niche is protected from the effects of chemotherapy. Those that survive acquire a survival advantage, and often become resistant to the same chemotherapeutic applied upon relapse. Thus, for those experiencing relapse, the treatment options using chemotherapy are very limited. This proposal is a study of how integrins function in white blood cells and their contribution to the pathology of blood cancers. By understanding these details, we aim to develop new therapeutics to prevent the undesired attachment of leukemic white blood cells in cancer, or find novel agents that ignores the protective effects for those attached via integrins. The intended outcome is lowering the chances for tumour relapse while effectively targeting the cancer with greater precision.