Bacteria-cancer interactions: bacteria-based cancer therapy

Abstract

Recent advances in cancer therapeutics, such as targeted therapy and immunotherapy, have raised the hope for cures for many cancer types. However, there are still ongoing challenges to the pursuit of novel therapeutic approaches, including high toxicity to normal tissue and cells, difficulties in treating deep tumor tissue, and the possibility of drug resistance in tumor cells. The use of live tumor-targeting bacteria provides a unique therapeutic option that meets these challenges. Compared with most other therapeutics, tumor-targeting bacteria have versatile capabilities for suppressing cancer. Bacteria preferentially accumulate and proliferate within tumors, where they can initiate antitumor immune responses. Bacteria can be further programmed via simple genetic manipulation or sophisticated synthetic bioengineering to produce and deliver anticancer agents based on clinical needs. Therapeutic approaches using live tumor-targeting bacteria can be applied either as a monotherapy or in combination with other anticancer therapies to achieve better clinical outcomes. In this review, we introduce and summarize the potential benefits and challenges of this anticancer approach. We further discuss how live bacteria interact with tumor microenvironments to induce tumor regression. We also provide examples of different methods for engineering bacteria to improve efficacy and safety. Finally, we introduce past and ongoing clinical trials involving tumor-targeting bacteria. Live tumor-targeting bacteria can selectively induce cancer regression and, with the help of genetic engineering, be made safe and effective vehicles for delivering drugs to tumor cells. In a review article, Jung-Joon Min and colleagues from Chonnam National University Medical School in Hwasun, South Korea, discuss the clinical history of using natural or engineered bacterial strains to suppress cancer growth. Because bacteria such as Salmonella and Listeria preferentially home in on tumors or their surrounding microenvironments, researchers have harnessed these microbial agents to attack cancer cells without causing collateral damage to normal tissues. Bioengineers have also armed bacteria with stronger tumor-sensing and more targeted drug delivery capabilities, and improved control of off-target toxicities. An increasing number of therapeutic bacterial strains are now entering clinical testing, promising to enhance the efficacy of more conventional anticancer treatments.