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Breast cancer clinical trial tests combo of heat shock protein inhibitor and hormonal therapy
Date:5/22/2012

therapy, long-term remission is uncommon and life expectancy is about three years. Currently, these patients have few therapeutic options. By adding an HSP90 inhibitor, Lin and Whitesell hope to hobble the resistant cancer cells, making them less likely to escape the effects of fulvestrant.

Lin likens a malignant tumor to a car on a highway in a high-speed chase. As the car hurtles down the road, police may erect a roadblock to stop it. In the case of ER+ breast cancer, that roadblock is hormonal therapy. Unfortunately, a tumor may mutate enough to find a detour around the roadblock and continue on its destructive course. Adding a heat shock protein inhibitor to the mix may thwart the cancer's ability to find an alternate route.

"Because of the way HSP90 inhibitors work, it's like throwing a bunch of roadblocks across a bunch of detours," says Lin, who will be running the clinical part of the trial. "So the idea is to try to block these alternative pathways that might allow the tumor to grow."

"Inhibiting HSP90 in tumors may not cause them to roll over and die," says Whitesell, who with support from Susan G. Komen for the Cure will be analyzing blood and tissue samples from trial participants. "But it may change the biology of the cancer to make it more susceptible to other things that we already know work against the cancer, like fulvestrant."

The trial's premise is based on years of work the Lindquist lab has conducted on heat shock proteins. That experience is invaluable, according to Sandro Santagata, a pathologist in the Lindquist lab who will also be examining patient tissue samples.

"The Lindquist lab has a great basic scientific understanding of the biology of the heat shock system," says Santagata. "That foundation will hopefully provide important insights to increase the likelihood of success for this trial and if it doesn't work, an understanding of why. That's always a tricky part. Figuring out the 'why' i
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Contact: Nicole Giese Rura
rura@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

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