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Study supports DNA repair-blocker research in cancer therapy
Date:8/17/2009

BOSTON--Scientists at Dana-Farber Cancer Institute have uncovered the mechanism behind a promising new approach to cancer treatment: damaging cancer cells' DNA with potent drugs while simultaneously preventing the cells from repairing themselves.

The findings being reported in the Aug. 14 issue of Molecular Cell help explain the promising results being seen in clinical trials of compounds that force cancer cells with genetic damage to self-destruct instead of "resting" while their DNA undergoes repairs.

"What we have shown suggests that you can use these drugs to sensitize cancer cells to DNA-damaging chemotherapy," said Geoffrey Shapiro, MD, PhD, senior author of the report. "This is a mechanism by which these inhibitory drugs may be synergistic with DNA-damaging agents."

Interestingly, Shapiro said, when the same repair-blocking drugs were administered to normal, non-cancerous cells, the cells became less sensitive to DNA damage from a chemotherapy drug. This is an encouraging indication that repair-blocking drugs may selectively make cancer cells vulnerable to chemotherapy while protecting normal cells from DNA damage, the scientists said.

Cells' native capacity for fixing DNA damage is normally beneficial, but it can be problematic for cancer therapy as it enables tumor cells to become resistant to a number of standard drug agents. All cells progress through a series of phases -- called the cell cycle -- including quiescence, or resting, growth, and cell division. The transition from one phase to the next is regulated by "checkpoint" proteins that, among other things, are designed to prevent damaged, potentially dangerous cells from reproducing.

The body deals with DNA-damaged cells in two ways. It can order them to self-destruct through "programmed cell death," also known as apoptosis. Or, it can issue signals from the checkpoint proteins to put the cells into "cell cycle arrest," causing them to remain q
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert

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