Bugging tumors.

The effects of bacteria on patients with cancer have been observed for at least two centuries. Recent studies in animal models of cancer have shown efficacy of both anaerobic bacteria such as Clostridia and Bifidobacteria and facultative anaerobes such as Salmonella. In this issue of Cancer Discovery, Flentie and colleagues have identified five Salmonella promoters that are specifically stimulated by cancer cells as well as by acidic pH, a property of most tumors. One of these promoters (STM1787) was linked to a Shiga toxin gene and inserted in a wild-type Salmonella typhimurium strain, which showed in vivo antitumor efficacy. Approaches to further improving the efficacy of S. typhimurium with the use of tumor-targeting mutations are discussed. Because the barriers to efficacy of standard therapy of cancer appear to be opportunities for bacterial cancer therapy, the future of bacterial therapy of cancer appears bright.