Cancer Drug Works by Overactivating Cancer Gene
News Nov 23, 2007
University of Michigan Comprehensive Cancer Center researchers have discovered that bortezomib, a promising cancer drug, is able to strike a blow against melanoma tumor cells by revving up the action of a cancer-promoting gene.
At top are healthy melanoma cells. Below, tumor cells treated with bortezomib show membrane outgrowths that are the hallmark of cell death. They say the laboratory-based findings suggest a novel treatment strategy that might someday prove effective against many types of cancer: Push cancer cells into overdrive, so that they self-destruct.
The U-M scientists found that bortezomib, a drug approved by the FDA to treat advanced multiple myeloma, is able to selectively inhibit melanoma tumor cells because it causes the c-MYC oncogene to overproduce a cell-death promoter called NOXA. Their results place c-MYC and NOXA, well studied among cancer researchers, in a new light. The study appears online ahead of print in the Proceedings of the National Academy of Sciences
“Our data suggest a different approach to treat cancer,” says Maria S. Soengas, Ph.D., the senior author of the study. Soengas is an assistant professor of dermatology at the U-M Medical School and a member of the U-M Comprehensive Cancer Center.
Many cancer treatments aim to block specific oncogenes, genes that wreak havoc with the normal signals that dictate when cells multiply and die.
The thinking is that if oncogenes are disabled, cancer cells can’t proliferate uncontrollably and spread. However, scientists know that oncogenes can play dual roles: They can cause tumor cells to rapidly divide, but can also step up programmed cell death, or apoptosis.
Therefore, “an alternative treatment could be to actually exacerbate oncogene function, to promote such a dysregulation of cell cycle progression and activation of apoptotic proteins that tumor cells ultimately die,” says Soengas.
In treating inflammatory bowel disease (IBD), physicians can have a hard time telling which newly diagnosed patients have a high risk of severe inflammation or what therapies will be most effective. Now researchers report finding an epigenetic signature in patient cells that appears to predict inflammation risk in a serious type of IBD called Crohn’s disease.