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Discovery: Overactive Breast Cancer Genes

June 6, 2011

(Ivanhoe Newswire) — Scientists have identified an overactive network of genes that drive certain cancer cells enriched in triple-negative breast tumors.

Triple-negative breast cancers are characterized by a lack of estrogen, progesterone and HER2 receptors, which makes them unresponsive to targeted treatments that block those receptors. These tumors make up about 15 to 20 percent of breast cancers and tend to occur in younger women, those with BRCA1 gene mutations and black women.

Researchers from the Dana-Farber Cancer Institute found a large proportion of cells within triple-negative breast tumors showed elevated activity in a network of genes called the Jak2/Stat3 pathway. Experiments have shown that a drug specifically targeted to block this pathway halts the growth of these tumors in mice.

The investigators surveyed genes present in the stem-like breast cancer cells, labeled CD44+CD24 cells, and found 1,576 genes that differed from those in other, more differentiated epithelial cancer cells within tumors.

Additional experiments assessing the viability of the stem-like breast cancer cells narrowed the field to 15 genes that were required for their growth and thus looked like promising targets for selective drugs. Those 15 genes were linked to the overactive Jak2/Stat3 pathway, which in turn, was triggered by a growth factor signal, interleukin-6.

“The discovery of these targets will rapidly lead to clinical trials with the hope of achieving one of the first specific therapies for triple-negative breast cancers,” Kornelia Polyak, M.D., Ph.D., a breast cancer geneticist at Dana-Farber, was quoted as saying.

SOURCE: The Journal of Clinical Investigation, July 2011




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