Research Project

Summary

Cancer is a major cause of human death worldwide. The vast majority of cancer patients suffer from solid tumors whose growth destroys vital organs. This project proposes to develop novel therapeutic drugs that target solid tumors affecting the brain, colon and ovaries. These cancers account for a significant proportion of currently intractable solid malignancies. Scientists have made great strides in understanding the molecular and cellular changes that cause cancer but the approval of new therapeutics that can specifically kill cancer cells has lagged behind. This disparity suggests that there must be critical bottlenecks impeding the process of turning a basic research discovery into a finished anti-cancer drug.

Research over the past decade has given rise to the idea that one of these bottlenecks may be caused by the existence of cancer stem cells. According to the cancer stem cell hypothesis, there is a minor population of cancer stem cells that drives the growth of the entire tumor. However, cancer stem cells are very rare and hard to identify. Technical innovations have recently allowed the identification, isolation and growth of these cells in the laboratory, and it has become clear that they have properties that are distinct from both the bulk of tumor cells and the cancer cell lines usually used to test anticancer drug candidates. Furthermore, in the lab, cancer stem cells are resistant to the chemotherapy and radiation treatments used to kill most tumor cells. In a patient, cancer stem cells may not be killed by standard drugs and may eventually regrow the tumor, causing a cancer to relapse or spread. Thus, a drug that specifically targets cancer stem cells could dramatically improve the chances of treatment success.

This team of Canadian and Californian researchers is one of the few in the world that can identify cancer stem cells in brain, colon and ovarian tumors. Furthermore, they have developed assays that can accurately test the effectiveness of drug candidates in killing these cells. Their preliminary data suggest that their lead drug candidates can inhibit the growth of cancer stem cells in culture and block tumor initiation in animal models. Importantly, their drug candidates appear to work through mechanisms that are different from those employed by current chemotherapeutics, meaning that their drugs represent a fresh and potentially very effective approach to cancer treatment. Over the next several years, the team proposes to complete the development and preclinical studies of these drugs so that testing in cancer patients can begin.