Integration of Salmonella into Combination Cancer Therapy

SIMPLE SUMMARY: Despite significant advances in the development of new treatments, cancer continues to be a major public health concern due to the high mortality associated with the disease. The introduction of immunotherapy as a new modality for cancer treatment has led to unprecedented clinical responses, even in terminal cancer patients. However, for reasons that remain largely unknown, the percentage of patients who respond to this treatment remains rather modest. In the present article, we highlight the potential of using attenuated Salmonella strains in cancer treatment, particularly as a means to enhance therapeutic efficacy of other cancer treatments, including immunotherapy, chemotherapy, and radiotherapy. The challenges associated with the clinical application of Salmonella in cancer therapy are discussed. An increased understanding of the potential of Salmonella bacteria in combination cancer therapy may usher in a major breakthrough in its clinical application, resulting in more favorable and durable outcomes. ABSTRACT: Current modalities of cancer treatment have limitations related to poor target selectivity, resistance to treatment, and low response rates in patients. Accumulating evidence over the past few decades has demonstrated the capacity of several strains of bacteria to exert anti-tumor activities. Salmonella is the most extensively studied entity in bacterial-mediated cancer therapy, and has a good potential to induce direct tumor cell killing and manipulate the immune components of the tumor microenvironment in favor of tumor inhibition. In addition, Salmonella possesses some advantages over other approaches of cancer therapy, including high tumor specificity, deep tissue penetration, and engineering plasticity. These aspects underscore the potential of utilizing Salmonella in combination with other cancer therapeutics to improve treatment effectiveness. Herein, we describe the advantages that make Salmonella a good candidate for combination cancer therapy and summarize the findings of representative studies that aimed to investigate the therapeutic outcome of combination therapies involving Salmonella. We also highlight issues associated with their application in clinical use.