Drugs that switch CHD5 may treat multiple types of cancer.

Researchers at Cold Spring Harbor Laboratory (CSHL) say they discovered a gene that not only acts as a tumor suppressor but also as a master switch for a tumor suppressive network. CSHL associate professor Alea Mills, Ph.D., thus predicts more targeted and effective cancer therapies in the future.

The scientists identified CHD5 as a protein that acts as a novel tumor suppressor and maps to a specific portion of chromosome 1 known as 1p36. When CHD5 is not functioning properly the machinery within our cells that normally prevents cancer turns off.

They believe that the ability of CHD5 to function as a master switch for a tumor suppressive network suggests that this gene is responsible for diverse forms of human cancers.

After locating the region where the tumor suppressor resided, the team identified which genes in that area were responsible for tumor suppression. Results showed that reducing expression of a single gene, CHD5 , made cells that had been rendered slow growing by adding an extra copy of the region, grow like normal cells.

The findings show that deletion of a part of 1p36 causes cancer, and increased “dosage” of CHD5 triggers extra tumor suppression. An extra dose, or copy, caused cells to either stop dividing or to undergo cell suicide by switching on a battery of potent tumor protective machinery.

The researchers say that this work indicates that pharmaceuticals that switch on CHD5 may provide a way to treat many types of human cancer.

The study was published in the February issue of Cell. The research team worked with mouse models so they could investigate gains and losses of the chromosome segment corresponding to human 1p36. To extend the research to human cancer, Dr. Mills collaborated with Stanford University researchers Hannes Vogel, M.D., and Markus Bredel, M.D., Ph.D., to study whether CHD5 also functioned as a tumor suppressor in humans. They discovered that glioma, a specific form of brain tumor, frequently had deletion of CHD5 , demonstrating the important role of CHD5 in human cancer.

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