BOSTON--The genomic tumult within tumor cells has provided scientists at Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard with clues to an entirely new class of genes that may serve as an Achilles' heel for many forms of cancer.
As reported in the Aug. 17 issue of the journal Cell, the researchers identified 56 such genes, only a few of which had previously been identified as potential targets for cancer therapy. Unlike most such targets, these genes don't cause normal cells to turn cancerous. Instead, they are essential to all cells but have been disrupted as cancer progresses.
"One of the hallmarks of cancer is genomic instability, in which entire sections of chromosomes can be lost or duplicated many times over," says Dana-Farber's Rameen Beroukhim, MD, PhD, who co-led the study. "The result is that genes residing in those areas are either deleted or significantly over-copied."
This roiling of the chromosomes often leads to partial loss of essential genes, leaving cancer cells with barely enough of these genes to survive. Such genes become lifelines for tumor cells. Blocking them with drug molecules is far more likely to harm cancer cells than normal cells.
One way that cancers lose these essential genes is by the loss of nearby tumor suppressor genes, which act as a brake against runaway cell growth. Whereas normal cells harbor two copies of each gene, cancers often lose at least one copy of important tumor suppressor genes, unleashing cell proliferation.
"When tumor suppressor genes are lost, it's common for several nearby genes -- which play no role in cancer development -- to be lost as well," explains the study's co-senior author William Hahn, MD, PhD, of Dana-Farber. Nearly 20 years ago, a scientist published a theory that blocking the remaining copies of these neighboring genes would cripple cancer cells' ability to grow and divide.
The author of that paper, in 1993,
|Contact: Anne Doerr|
Dana-Farber Cancer Institute