September 27, 2012

Target acquired for aggressive tumor

New therapeutic target for angiosarcoma – an aggressive, highly fatal tumor of the blood vessels – identified.

(Wikimedia Commons)

Angiosarcoma, a rare, aggressive tumor that arises from cells that line blood vessels, has a mortality rate of around 80 percent. Because of their constant contact with the blood stream, these tumors can spread quickly and freely throughout the body.

The INK4a/ARF locus on chromosome 9 – a region that encodes tumor suppressor proteins – is frequently inactivated in human angiosarcomas. Using mice genetically engineered to lack the Ink4a/Arf gene, Ann Richmond, Ph.D., Ingram Professor of Cancer Research, Jinming Yang, Ph.D., and colleagues found that disruption of this gene resulted in spontaneous angiosarcoma formation in multiple organs, which was accompanied by activation of the Ikk-beta signaling pathway. Unexpectedly, inhibiting Ikk-beta in immune cells alone stimulated tumor growth, showing that Ikk-beta may be important for anti-tumor responses in myeloid cells. However, systemic inhibition of Ikk-beta or other components of the pathway markedly inhibited tumor growth.

The findings, reported Sept. 7 in Cancer Research, suggest that the Ikk-beta pathway represents an important and much needed therapeutic target for angiosarcoma.

The research was supported by grants from the National Cancer Institute (CA116021, CA068485) of the National Institutes of Health and the Department of Veterans Affairs.