Chemotherapy 2.0: Targeted anti-cancer treatments

Dr. Sandra Turcotte, Atlantic Cancer Research Institute. Photo courtesy of Martin Wightman.

The next generation of anti-cancer treatments is getting personal

March 17, 2016

Since their introduction in the 1940s, conventional chemotherapy drugs have been widely used as cancer treatment due to their ability to target rapidly-dividing cancer cells. However, chemotherapy is more of a buckshot method of eradicating cancer cells, rather than a targeted one, as the drugs are equally toxic to healthy cells, creating substantial collateral damage.

Researchers know that not all cancers respond to chemotherapy in the same way, if at all. A molecular understanding of why certain cancer cells respond to a specific type of chemotherapy, while others are resistant, is a puzzling phenomenon that remains largely unexplained.

Dr. Sandra Turcotte, researcher in Residency at the Atlantic Cancer Research Institute and a biochemistry professor at the University of Moncton, is leading a team of researchers that are making important inroads in uncovering the next generation of targeted cancer fighting drugs.

Specializing in renal cell carcinoma, commonly known as kidney cancer, she is well aware that advanced stage renal tumors are resistant to treatments that use conventional chemotherapy. Knowing that a better solution is needed, Dr. Turcotte is seeking to harness the power of "synthetic lethality".

Dr. Sandra Turcotte, Atlantic Cancer Research Institute
Reproduced with permission from the University of Moncton

Based on the ancient Greek meaning of synthetic as the combination of two entities forming something new, the term "synthetic lethality" is used to describe situations when two or more cellular mutations turn lethal when they occur simultaneously within the same cell. The result is the death of the host cell or organism.

So in the case of a chemotherapy drug, while neither the cellular mutation nor the drug alone is lethal, when put together, the cancer cell is doomed.

The power to identify new, synthetic lethal interactions holds much promise and would be an invaluable tool for physicians, broadening their choice of available cancer therapies.

This new generation of targeted anticancer therapies, or TATS, has attracted the attention of researchers like Dr. Turcotte and, while her particular area of interest is fighting renal cell carcinoma, she is convinced that the possibilities of synthetic lethality are endless.

Dr. Turcotte's unique approach to the problem is to discover the particular role played by the von Hippel–Lindau protein (VHL) as a gatekeeper that prevents renal cancer from developing.

When the VHL gene is inactivated, or mutated, it causes a variety of tumors, including clear cell renal cell carcinoma. Through their research, Dr. Turcotte and her team have discovered a new molecule, STF-62247, and are exploring what happens if the loss of VHL is combined with this newly discovered molecule to stimulate synthetic lethality.

With her CIHR funding, Dr. Turcotte and her team continue to explore how to refine the process in order to develop viable anti-cancer treatment therapies. It is hoped that one day, this new discovery will make its way from their laboratories at the Atlantic Cancer Research Institute to treatment centres around the world.

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