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The preclinical discovery of bacterial therapy for the treatment of metastatic cancer with unique advantages

Introduction: The potential of bacteria as therapeutics for cancer has a long history, dating at least as far back as the early 19th Century. Bacteria have a large genome that can be manipulated in order to target and eradicate tumors. Many types of bacteria have been shown to target tumors but most are obligate anaerobes whose growth is confined to the necrotic parts of tumors, thereby limiting their efficacy. Salmonella, on the other hand, are facultative aerobes that can grow aerobically or anaerobically and, therefore, grow on viable tumor tissue as well as necrotic tissue. Areas covered: The article focuses on the double amino-acid auxotrophs of Salmonella typhimurium. These auxotrophs, which have no attenuating mutations and can grow in both viable and necrotic areas of tumors but not normal tissue, have shown particular effectiveness in mouse models of metastatic cancer. The approach described here is a significant improvement over previous bacterial tumor-therapy strategies which must be combined with toxic chemotherapy in order to be effective. This review uniquely discusses the critical points to optimally engineer Salmonella typhimurium for cancer therapy. Expert opinion: Bacterial therapy offers significant advantages over chemical or biological drugs or oncolytic viruses. Of these types of bacterial therapy, bacteria that can grow in both viable and necrotic areas of the tumors without growing in normal tissue hold the greatest promise in the treatment of cancer. Salmonella typhimurium shows much promise for this paradigm.