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Tumor cells seek temporary shelter from cancer drugs
Date:4/1/2010

Results reported in the April 2nd issue of the journal Cell, a Cell Press publication, reveal a new source for the drug resistance that crops up all too often and quickly in the tumors of cancer patients undergoing therapy. First the bad news: all cancer cells might have the capacity to enter a drug-tolerant state. But there's some potentially very good news too: in some cases there may be a way to reverse or block cancer's drug resistance.

"The problem with cancer drug therapy is that even the ones that work well generally only work for a limited time because drug resistance develops," said Jeff Settleman of Harvard's Massachusetts General Hospital Cancer Center.

Scientists have thought that resistance primarily stems from genetic causes mutations in some tumor cells that may have pre-existed drug treatment. The theory holds that those drug-resistant mutants rise in prevalence with treatment as a classic example of survival of the fittest. "We're suggesting here that, while that may occur, there may be other non-genetic mechanisms [for drug resistance] that serve as a way to protect the tumor as a whole in a somewhat purposeful way," Settleman added.

While examining the acute response of human tumor cells in culture to various anti-cancer agents, Settleman and his colleague Marie Classon consistently detected a small subpopulation of reversibly "drug-tolerant" cells. Those cells were more than 100 times less sensitive to cancer drugs. They also found that the cells' drug tolerant state was transiently acquired and relinquished at low frequency by individual cells within the culture population.

The researchers don't yet know exactly how the cells manage that kind of reversible drug resistance, but they did uncover a couple of key features: the cells engage a signaling pathway including the IGF-1 receptor (which is a tyrosine kinase receptor) and their genetic material was also packaged differently into its three-di
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Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

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