Grant: CIHR Fellowship

Background: Despite major advances in basic cancer research the treatment of cancer particularly advanced metastatic disease remains a formidable challenge. This is partly due to the fact that although treatment of many types of cancer with conventional chemotherapy regimens often results in partial or complete tumour shrinkage, this is almost always followed by rapid tumour regrowth. In this regard, studies from our laboratory have been particularly relevant. For example, we have shown that the overall anti-tumour impact of certain commonly used anti-cancer drugs is accompanied by a rapid reaction and systemic host response that acts to reduce anti-tumour effects. This response includes induction of a number of tumour growth promoting factors and circulating bone marrow-derived cell populations, in such a way as to increase the tumour's ability to 'recover' more quickly from the anti-cancer therapy. Objectives of the Research Proposal: The overall aim of my research is to identify the mechanisms involved in this 'counter-active' host response leading to accelerated tumour regrowth, such that we can develop better ways to enhance the impact of anti-cancer treatments. Brief Description of the Research Proposal: With respect to the growth factors that are induced by chemotherapy, we are studying the sources of such factors, e.g. what cells are responsible for rapidly releasing these factors when exposed to chemotherapy drugs. In order to accomplish this, we will use preclinical models in conjunction with the same chemotherapy drugs used to treat cancer patients. We will monitor the effects of these anti-cancer agents in the models and employ treatment strategies to enhance their anti-cancer effect while reducing the negative 'counter-acting' response. These approaches will include reducing the doses of chemotherapy drug administered and combining conventional chemotherapy with drugs that target the growing tumours blood vessel supply.