Bacteria and genetically modified bacteria as cancer therapeutics: Current advances and challenges

Bacteria act as pro- or anti- tumorigenic agents. Whole bacteria or cytotoxic or immunogenic peptides carried by them exert potent anti-tumor effects in the experimental models of cancer. The use of attenuated microorganism(s) e.g., BCG to treat human urinary bladder cancer was found to be superior compared to standard chemotherapy. Although the phase-I clinical trials with Salmonella enterica serovar Typhimurium, has shown limited benefits in human subjects, a recent pre-clinical trial in pet dogs with tumors reported some subjects benefited from this treatment strain. In addition to the attenuated host strains derived by conventional mutagenesis, recombinant DNA technology has been applied to a few microorganisms that have been evaluated in the context of tumor colonization and eradication using mouse models. There is an enormous surge in publications describing bacterial anti-cancer therapies in the past 15 years. Vectors for delivering shRNAs that target oncogenic products, express tumor suppressor genes and immunogenic proteins have been developed. These approaches have showed promising anti-tumor activity in mouse models against various tumors. These can be potential therapeutics for humans in the future. In this review, some conceptual and practical issues on how to improve these agents for human applications are discussed.