New anti-inflammatory strategy for cancer therapy identified by UCSD researchers

A new strategy for cancer therapy, which converts the tumor-promoting effect of the immune system's inflammatory response into a cancer-killing outcome, is suggested in research findings by investigators at the University of California, San Diego (UCSD) School of Medicine.

The findings provide new insight into the immune system's response to inflammation, the connection between inflammation and malignancy, and how the delicate balance between cancer promotion and inhibition can be manipulated in the patient's favor, according to the study's senior author, Michael Karin, Ph.D., UCSD professor of pharmacology, American Cancer Society Research Professor, and a member of the Rebecca and John Moores UCSD Cancer Center.

The studies in mice with colon or breast cancer showed that cancer metastasis, the growth of malignant tumors beyond the original site, was halted with inhibition of either one of two naturally occurring substances, a pro-inflammatory protein called nuclear factor-kappa B (NF-kB) or an inflammatory mediator called tumor necrosis factor alpha (TNFα). The result, published in the September 20, 2004 issue of the journal Cancer Cell, was increased effectiveness of a cancer-killing protein called TNF-related apoptosis-inducing ligand (TRAIL), leading to a decrease in cancer cells and increase in the life span of tumor-bearing mice.

The study's first author, Jun-Li Luo, M.D., Ph.D., a member of the Karin team in the UCSD Laboratory of Gene Regulation and Signal Transduction, explained that normally, inflammation associated with malignancy activates NF-kB, TNFα and TRAIL, all at the same time. However, NF-kB has the upper hand, and with TNFα, stimulates tumor growth faster than TRAIL can inhibit it.

"Our results suggest that is it possible to use NF-kB or TNFα inhibitors to prevent inflammation-induced tumor growth, thus destroying their advantage, and allowing TRAIL to tip the balance in its favor,"

Contact: Sue Pondrom
University of California - San Diego

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