Bacterial therapies: completing the cancer treatment toolbox.

Current cancer therapies have limited efficacy because they are highly toxic, ineffectively target tumors, and poorly penetrate tumor tissue. Engineered bacteria have the unique potential to overcome these limitations by actively targeting all tumor regions and delivering therapeutic payloads. Examples of transport mechanisms include specific chemotaxis, preferred growth, and hypoxic germination. Deleting the ribose/galactose chemoreceptor has been shown to cause bacterial accumulation in therapeutically resistant tumor regions. Recent advances in engineered therapeutic delivery include temporal control of cytotoxin release, enzymatic activation of pro-drugs, and secretion of physiologically active biomolecules. Bacteria have been engineered to express tumor-necrosis-factor-alpha, hypoxia-inducible-factor-1-alpha antibodies, interleukin-2, and cytosine deaminase. Combining these emerging targeting and therapeutic delivery mechanisms will yield a complete treatment toolbox and increase patient survival.