Dr. Susan P.C. Cole

Canada Research Chair in Cancer Biology, Tier I
Fellow of the Royal Society of Canada
Professor of Pathology & Molecular Medicine, Pharmacology & Toxicology, and Chemistry
Senior Scientist Cancer Care Ontario

Enhancing the Efficacy of Anti-Cancer Drugs and Protecting Normal Tissues Against Chemical Toxins

The development of multidrug resistance continues to be a substantial impediment to the successful treatment of many cancers. Scientists like Dr. Susan P.C. Cole, a professor with a primary appointment in the Department of Pathology & Molecular Medicine and member of the Cancer Biology & Genetics division of the Queen’s University Cancer Research Institute, firmly believe the key to resolving this challenge lies in research focused on identifying the biological mechanisms that prevent these drugs from exerting their toxic effects on cells. This information can then be used to develop new strategies to improving treatments for cancer patients.

One mechanism by which drug resistance occurs is by increased expression of proteins that act as drug efflux pumps on the plasma membranes of tumour cells, and prevent the toxic agent from accumulating to a concentration that is lethal to the cell. In 1992, Dr. Cole and her colleagues cloned a new multidrug resistance drug efflux pump, now known as MRP1, from drug resistant lung cancer cells. Subsequently, at least six other proteins related to MRP1 were discovered and together, the MRP family of drug resistance proteins have been shown to confer resistance to an extraordinarily broad range of structurally unrelated chemicals. The chemicals transported by the MRPs include not only anticancer drugs and therapeutic agents used to treat other diseases, but also chemicals found in the environment (e.g. tobacco-derived substances, herbicides, pesticides, carcinogens) and in the diet (bioflavonoids). The MRP transporters are found in most normal tissues (e.g. brain, liver, kidney, testis, etc.) where their normal function is to control the transport various physiologic molecules out of cells (e.g. GSH, leukotrienes, prostaglandins, folic acid). MRPs are also thought to play an important role in the defence of normal tissues against drugs and other chemicals.

One of Dr. Cole’s current goals is to elucidate the structural and molecular features of the MRPs that determine their remarkable ability to transport so many different chemical entities. A second major goal is to identify additional therapeutic agents, environmental chemicals and dietary components that are transported by MRP1 (and related proteins) or else modulate expression and/or activity of the MRP transporters.

Because of the fundamental role that MRP and other transporters play in drug action and toxicity, knowledge of whether or not new drug candidates interact with these proteins is important information to be acquired during the process of drug discovery and development by pharmaceutical and biotechnology companies alike. Dr. Cole and her collaborator Dr. Roger Deeley have worked with several private sector institutions to develop agents that can reverse resistance mediated by MRP1 and to better define the roles of the MRP proteins in drug efficacy.

Dr. Cole’s internationally recognized efforts in furthering our molecular understanding of drug resistance and drug/chemical transport in and out of cells have earned her a number of awards including election as a fellow to the Royal Society of Canada (2000) and a Tier 1 Canada Research Chair in Cancer Biology (2001). Her research is funded by the Canadian Institutes of Health Research and by the Canadian Cancer Society through the National Cancer Institute of Canada.

For further information, please contact Dr. Susan P.C. Cole using the Email contact form or by phone at 613 533-2636