New Test Predicts Blood Cancers Sensitivity to Experimental Cancer Drug
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A test developed by Dana-Farber Cancer Institute scientists is claimed to be the first to identify which malignant blood cells are highly vulnerable to a promising type of experimental drugs that unleash pent-up cell suicide factors to destroy the cancer.
The researchers demonstrated that chronic lymphocytic leukemia, CLL, which is diagnosed in 10,000 Americans each year, is an easy mark for the drug because the cancerous cells are strongly dependent on a particular survival molecule, Bcl-2, that keeps the self-destruct signals at bay.
The researchers showed that the investigational drug neutralizes the Bcl-2 action, unleashing molecules that trigger suicide in the cancer cells, a process known as programmed cell death or apoptosis.
The research in the laboratory of Anthony Letai, MD, PhD, of Dana-Farber, is described in the January issue of The Journal of Clinical Investigation. The lead author is Victoria Del Gaizo Moore, PhD, a member of the Letai group.
Letai was a colleague of the late Stanley J. Korsmeyer, MD, of Dana-Farber, who discovered the key role in cancer played by anti-apoptosis molecules such as Bcl-2, which promote the survival of cells that are damaged or abnormal despite the body’s efforts to eliminate them through apoptosis.
Letai said that his group has tested Abbott's investigational compound ABT-737 against cultured CLL cells with striking results.
"We've treated CLL samples from several dozen patients, and each has responded to a very low concentration of the drug," said Letai. "We find it particularly interesting that the cells died within four hours."
"It's essential to figure out which cancers are going to respond to the drug by identifying the cells that are dependent on Bcl-2 for survival," said Letai, who is also an assistant professor of medicine at Harvard Medical School. "Up to now there hasn't been a way to do this."
The paper's co-authors are Jennifer R. Brown, MD, PhD, Michael Certo, Tara M. Love, PhD, and Carl D. Novina, MD, PhD, all of Dana-Farber.
The research was funded by the National Institutes of Health, the Dunkin Donuts Rising Stars Program, the Richard and Susan Smith Family Foundation, and the Sidney Kimmel Foundation for Cancer Research.
