Grant: Banting Postdoctoral Fellowship Program

One in two Canadians will develop cancer in their lifetime and one in four will die, mostly due to tumours spreading to other sites of the body (metastasis). Cancer therapies that inhibit the growth of new blood vessels into tumours have known, but limited effectiveness when treating patients with metastasis. This is partly due to tumour cells bypassing the need of creating their own blood supply and instead hijacking the existing blood vessels in organs with a rich vasculature such as the lung - one of the most common sites of metastatic disease in cancer patients. This process is called "vessel co-option" and in the lung leads to the striking phenomenon of tumour cells filling up the air spaces to exploit the organ's existing blood supply. We propose strategies to target such co-opted vessels in lung metastases. There is a high probability that since co-opted vessels are exposed to many changes brought about by the tumour, they express proteins that are not normally found on healthy blood vessels, and which may be therapeutically targetable. We have developed a mouse model of breast cancer metastasis that mimics cancer observed in human patients. In this model vessel co-option happens exclusively when metastasis occurs in the lung. To determine differences in co-opted versus normal vessels, cells of the co-opted blood vessels will be isolated from lung metastases and undergo gene expression analysis in comparison to vessels from normal healthy lungs. Drugs will be generated that target these differences on hijacked vessels with the goal of destroying them. There are also a number of carefully selected existing drugs and experimental therapies which may have the property of targeting vessel co-option, and these will be evaluated. Such vessel co-option targeting therapies could be used in combination with drugs that stop the growth of new blood vessels to block two major ways a tumour gains a blood supply, in turn starving the tumour and arresting its growth.