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Distinguishing friend from foe in the battle against cancer

The latest generation of cancer chemotherapeutic drugs specifically targets mutant enzymes or "oncoproteins" that have run amok and now promote uncontrolled cell growth. As promising as these drugs are, cancer cells with their backs against the wall have the tendency to fight back. A major goal of cancer research is to frustrate these acts of cellular desperation.

In a forthcoming issue of Cancer Cell, investigators at the Salk Institute for Biological Studies uncover one means cancer cells use to stay alive and in doing so suggest a strategy to overcome their recalcitrance. The study, led by Tony Hunter, Ph.D., in collaboration with Inder Verma, Ph.D., shows that resistance to the chemotherapeutic drug rapamycin is mediated by the survival factor NF-kB.

Rapamycin, like the pharmaceutical superstar Gleevec, which revolutionized the treatment of chronic myelogenous leukemia, is a so-called signal transduction inhibitor or STI, a small molecule that stifles inappropriate growth signals sent by mutant proteins in cancer cells. STIs may look like overnight successes, but they are actually the result of decades of hard work.

"We have been working for 35 years looking at mechanisms underlying formation of cancer cells," says Hunter, an American Cancer Society professor in the Molecular and Cell Biology Laboratory. "We've made huge progress identifying specific events that change normal proteins into proteins that cause cancer and developing drugs that target those proteins. This work provides another potential direct target for development of cancer drugs."

The Hunter lab previously showed that mouse cells lacking tumor suppressors known as TSC genes are more susceptible to the lethal effects of chemotherapeutic agents than are normal cells. Why cells from these TSC null mice were so poorly equipped to survive was not entirely clear.

Co-lead authors Sourav Ghosh, Ph.D., and Vinay Tergaonkar, Ph.D., postdoctoral fellows in the respe
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Source:Salk Institute


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