Sep 7, 2012

Study Finds New Ways Cells Respond to DNA Damage From Chemotherapy Drugs

Grant Brown

A group of Toronto scientists, led by University of Toronto Faculty of Medicine Professor Grant Brown, have discovered new ways that cells respond to the damage caused by chemotherapy, a finding that could improve treatments for patients. While chemotherapy can kill cancer cells, it can also harm healthy cells. This leads to side effects such as hair loss, fatigue, nausea and a weakened immune system.

Understanding how both normal cells and cancer cells deal with DNA damage is instrumental in improving patient treatment. “In a cell there’s never only one response but a multitude of responses,” says Brown, a principal investigator at the Terrence Donnelly Centre for Cellular and Bimolecular Research and an associate professor in the department of biochemistry. “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.”

In this Canadian Cancer Society–funded study, Brown’s team used a microscopic screening technology to study cell proteins and their responses to specific chemotherapy drugs.

This is the first time cell proteins have been studied in this way, allowing scientists to better understand what happens inside a cell during chemotherapy. Brown’s group found that, during chemotherapy, hundreds of proteins move to new locations in the cell or multiply. They studied how the cellular proteins move in real time by tagging them with a fluorescent molecule. 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 sets of proteins respond differently to chemotherapy drugs and that there are many ways that the cell tries to combat DNA damage. Brown hopes others will use a similar 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.