Enzyme Links Inflammation and Tumor Progression

A publication identified an enzyme that forms the link between inflammation and tumor growth.

Investigators at the University of California, San Diego (USA) studied the mechanisms that control tumor growth and inflammation by examining molecular signaling pathways that are commonly activated by multiple diverse tumor-derived chemical messengers.

The investigators reported in the June 14, 2011, issue of the journal Cancer Cell that results from experiments conducted with both mouse and human cells revealed that a single enzyme, PI3Kinase gamma, was the common element connecting a wide range of signaling pathways that controlled both tumor inflammation and progression.

Pharmacological or genetic blockade of PI3Kinase gamma suppressed inflammation, growth, and metastasis of implanted and spontaneous tumors, revealing an important therapeutic target. Growth inhibition occurred despite the absence of the enzyme in cancer cells. Suppression of tumor growth was due to blocking this enzyme in surrounding inflammatory cells. Since chemical inhibitors of PI3Kinase gamma do not act directly on tumor cells, it is not likely that these cells will develop resistance to the inhibitors.

"Our studies show that PI3Kinase gamma is an excellent target for cancer therapeutics, as this enzyme is primarily expressed in specific immune cells and is a gatekeeper of tumor inflammation and tumor progression," said senior author Dr. Judith A. Varner, professor of medicine at the University of California, San Diego. "We found that PI3Kinase gamma inhibitors strongly suppressed tumor growth and progression in mice without apparent side effects. Thus, selective inhibitors of PI3Kinase gamma could serve as relatively nontoxic therapeutics to suppress tumor malignancy by blocking diverse pathways promoting tumor inflammation. Targeting tumor inflammation could provide substantial therapeutic benefit to most, if not all, cancer patients."

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