Anti-Cancer Gene Kills Widely Dispersed Tumors

Cancer researchers have learned how a potential therapeutic agent, melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), is able to kill widely dispersed tumors without harming surrounding normal cells.

Investigators from Virginia Commonwealth University (Richmond, USA) used an adenovirus vector to transmit the mda-7/IL-24 gene into human tumors growing in an animal model. The mda-7/IL-24 protein produced by the gene triggered the cell death mechanism in the tumor cells by inducing an endoplasmic reticulum (ER) stress response. ER stress resulted from accumulation of extra proteins in the ER of the cancer cells.

Mda-7/IL-24 induced growth inhibition and apoptosis in surrounding cancer cells that had not been directly infected with the adenovirus vector but not in normal cells, thus exerting an anti-tumor "bystander” effect. The protein killed not only the tumor into which it had been injected, but also distant ones as well. These findings were published in the June 30, 2008, online edition of the Proceedings of the [U.S.] National Academy of Sciences (PNAS).

"Cancer cells cannot accommodate or recover from stress the way normal, healthy cells can. When the ER is stressed in this way, the result is an unfolded protein response, which overloads the system and shorts out the cancer cell. This prevents tumor development, growth and invasion--and ultimately the cancer cell dies,” said senior author Dr. Paul B. Fisher, professor of the human and molecular genetics at Virginia Commonwealth University.


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