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New study on chemotherapy drugs

01 August 2012

Lab head, Dr Grant Brown with first author of the study, Dr Johnny TkachAugust 2012 – Toronto scientists have discovered new ways that cells deal with the damage caused by chemotherapy, a finding that could improve treatments for patients.

A double-edged sword, chemotherapy can be very effective in killing cancer cells but it can also harm healthy cells and lead to numerous side effects, including hair loss, fatigue, nausea and a weakened immune system.

Understanding how both normal cells and cancer cells deal with DNA damage is instrumental in helping us improve patient treatment.

In this Canadian Cancer Society–funded study, the research team used a microscopic screening technology to study all the proteins in the cell and their response to specific chemotherapy drugs. This is the first time all the proteins in cells have been studied in this way, allowing scientists to better understand what happens inside a cell during chemotherapy.

The researchers found that hundreds of proteins move to new locations in the cell or increase in number during chemotherapy. They studied the movement of the cellular proteins by tagging them with a fluorescent molecule, which allowed the proteins to be tracked in real time under the microscope. The research team then treated the cells with different chemotherapy drugs and monitored them for changes in the location and abundance of the glowing proteins. They found that different sets of proteins respond in differing ways to chemotherapy drugs and there are many ways that the cell tries to combat DNA damage.

“In a cell there’s never only one response but a multitude of responses,” says Dr Grant Brown, the study’s lead investigator and a professor at the Donnelly Centre and the department of biochemistry at the University of Toronto. “Understanding these responses can tell us how normal cells counteract the damaging properties of cancer drugs and can show us targets that could make cancer cells more sensitive to chemotherapy.”

Dr Brown says the researchers are hoping that scientists can now use a similar comprehensive microscopic screening technique to study all types of cancer drugs. This will help scientists and clinicians make more informed decisions about drugs and improve therapy options for many types of cancer.

The study was released on nature.com and will be published in the September 2012 issue of the journal Nature Cell Biology.