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November 14, 2007

Synthetic Molecule Makes Cancer Cells Commit Suicide

Topics: Medical Science News

Scientists are now ... "SMAC-ing" cancer to death.

Apoptosis.jpgHoward Hughes Medical Institute researchers have developed a small molecule that can turn the survival signal for a variety of cancer cells into a death signal. The molecule mimics the activity of Smac (second mitochondria-derived activator of apoptosis), a protein that triggers the suicide of some types of cancer cells (an event known as apoptosis). The researchers believe their findings suggest that Smac-mimetic compounds could be useful as targeted cancer treatments for lung and other cancers. The therapy may be less toxic to healthy cells than current compounds used in cancer chemotherapy:

... In the new studies published in Cancer Cell, Wang and his colleagues found that a significant percentage of human non-small-cell lung cancer cell lines were sensitive to treatment by the Smac mimetic alone. When the researchers introduced those sensitive cells into mice and allowed them to produce tumors, they found that the Smac mimetic caused the tumors to regress and, in some cases, even disappear.

"These findings made us wonder what it was about these cell lines that made them sensitive to the Smac mimetic alone," said Wang. "Cancer cells are hard to kill, but these cell lines seemed to have already become sensitized to apoptosis."

The researchers' studies revealed that the sensitive cell lines produced their own TNFá (Tumor Necrosis Factor-a), so they were already "primed" for apoptosis. The paradox, said Wang, is that TNFá signaling is also part of a complex pathway that gives cancer cells a "survival" signal, offering them a growth advantage. The researchers also found that some breast cancer and melanoma cell lines were sensitive to the Smac mimetic alone.

"Thus, in these cancer cell lines, the TNFá survival advantage turns out to be a fatal flaw, because the same pathway can be switched to apoptosis by Smac mimetics," said Wang. "So, for some cancers, we might be able to use Smac mimetics as a single treatment agent. And we can use the presence of TNFá as a marker to tell us which tumors will respond to the Smac mimetic alone."

Continue reading, "Synthetic Molecule Makes Cancer Cells Commit Suicide."

Posted by Richard at November 14, 2007 9:33 AM

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