Cancer Society Supports Groundbreaking U of G Research

June 24, 2010 - News Release

A University of Guelph molecular and cellular biology professor who is studying how tumour cells become resistant to chemotherapy drugs has received an additional $370,000 over three years from the Canadian Cancer Society Research Institute. This funding builds on the nearly $713,000 Frances Sharom received from the national agency in 2005.

The funding will support Sharom’s groundbreaking research on a membrane protein involved in the resistance of tumours to drugs designed to kill them. When this phenomenon — known as multi-drug resistance — happens, cancer treatment fails.

Multi-drug resistance is a major problem in treatment of tumours of the colon, breast and kidney, as well as leukemias, multiple myeloma and childhood cancers. It’s the single greatest barrier to successful cancer chemotherapy treatment, so even a small reduction in drug resistance could save thousands of lives.

The Sharom research team is studying a protein pump called P-glycoprotein (Pgp) found in the cell membrane of some multi-drug-resistant tumour cells. Scientists believe the pump is important in non-cancerous cells in removing toxic compounds from the body. But in tumours, it also pumps out chemotherapy drugs, enabling the cells to survive and grow. Sharom hopes that, by identifying how this process works at the molecular level, her research could help solve the problem of cancer cells becoming drug-resistant. Her long-term goal is to develop new treatments for improving chemotherapy in drug-resistant forms of cancer.

The Pgp drug pump belongs to a large protein family first discovered in the early 1980s. Sharom’s research team was among the first to purify Pgp and begin biochemical studies on it in the 1990s. “Pgp contains an unusually large ‘pocket’ for binding drugs,” she said, adding that her research team has found that the pocket can accommodate two different drug molecules at once. They’re investigating where precisely each drug binds and how readily a second drug binds after the first one has been "pocketed." “This is important in clinical therapy because cancer patients are often treated with cocktails of several different chemotherapy drugs.” The Sharom group can track the pocketing process in milliseconds, using specialized instrumentation.

They are also investigating how cellular energy powers drug transport. “We have discovered a special form of Pgp that is ‘frozen’ at one stage of the transport process, which we can use to find out how energy input changes the shape of the protein.”

Sharom, who holds a prestigious Tier 1 Canada Research Chair in Membrane Protein Biology, uses novel biophysical and biochemical approaches to study membrane proteins important in health and disease. About one-third of all DNA sequences in the human genome encode membrane proteins, which are vital in cancer, genetic diseases such as cystic fibrosis, and bacterial and viral infections. Yet scientists know little about the structure of these proteins and how they work, she said.

Sharom has written more than 125 refereed journal articles and book chapters. She directed the Biophysics Interdepartmental Group at U of G from 2003 to 2008. She was president of the Canadian Society of Biochemistry, Molecular and Cellular Biology. Her work is also supported by the Natural Sciences and Engineering Research Council of Canada.

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