A report published on July 18 in the open-access journal PLoS Genetics describes a new approach to fighting cancer. Researchers have located a new type of ultrasensitive genes that seem to control the way cancer expresses itself (cancer-associated phenotypes). It is possible that the growth and survival or tumors and other disease-causing agents may be thwarted if drugs are developed that can target these genes.
Dr. Patrick Tan, M.D., Ph.D. (associate professor of Duke-NUS Graduate Medical School in Singapore) and colleagues looked through genetic data in cancerous and healthy tissues to find genes that did not vary much during their expression, or were “tightly controlled.” If the same genes were found in both tissue types, the researchers focused the search for genes that were more tightly controlled in cancerous tissues. Tissue samples came from lungs, livers, thyroids, esophagi, colons, and breasts.
Tan said, “We thought that since the tumors were spending costly cellular resources and energy to control the expression of these particular genes, they must have functional importance in cancer.” The investigation led to 48 tightly controlled genes, which the scientists called a “poised gene cassette” or PGC.
“We view the PGC genes as an exciting new class of genes, in which you would only need to slightly affect gene function to elicit a sizeable effect on the tumor,” notes Tan. “This would make the PGC genes attractive targets.” The researchers were able to demonstrate that small changes in PGC expression were linked to significant differences in experimental metastasis (how cancer spreads around the body) and patient survival. There was a direct functional role for five PGC genes related to cancer invasion.
Further, using PGC genes as a target in cancer treatment may only require a 10 to 20 percent inhibition in protein activity in order to be effective. This is an improvement compared to using other genes that may require a 90 to 100 percent inhibition in protein activity in order to see an effect on tumors. Finding that the PGC was not tightly regulated in noncancerous tissue also provided more evidence that the collection of genes is regulated in cancerous tissue.
“Beyond cancer, we could easily apply this approach to other diseases. With the right data, researchers could find genes related strictly to disease progression and explore how they can be manipulated to our benefit,” Tan concluded.
A Precisely Regulated Gene Expression Cassette Potently Modulates Metastasis and Survival in Multiple Solid Cancers
Yu K, Ganesan K, Tan LK, Laban M, Wu J, et al.
PLoS Genetics (2008). 4(7):e1000129.
doi:10.1371/journal.pgen.1000129
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Written by: Peter M Crosta