Abstract
Currently approximately 10 million people die each year due to cancer, and cancer is the cause of every sixth death worldwide. Tremendous efforts and progress have been made towards finding a cure for cancer. However, numerous challenges have been faced due to adverse effects of chemotherapy, radiotherapy, and alternative cancer therapies, including toxicity to non-cancerous cells, the inability of drugs to reach deep tumor tissue, and the persistent problem of increasing drug resistance in tumor cells. These challenges have increased the demand for the development of alternative approaches with greater selectivity and effectiveness against tumor cells. Cancer immunotherapy has made significant advancements towards eliminating cancer. Our understanding of cancer-directed immune responses and the mechanisms through which immune cells invade tumors have extensively helped us in the development of new therapies. Among immunotherapies, the application of bacteria and bacterial-based products has promising potential to be used as treatments that combat cancer. Bacterial targeting of tumors has been developed as a unique therapeutic option that meets the ongoing challenges of cancer treatment. In comparison with other cancer therapeutics, bacterial-based therapies have capabilities for suppressing cancer. Bacteria are known to accumulate and proliferate in the tumor microenvironment and initiate antitumor immune responses. We are currently well-informed regarding various methods by which bacteria can be manipulated by simple genetic engineering or synthetic bioengineering to induce the production of anti-cancer drugs. Further, bacterial-based cancer therapy (BBCT) can be either used as a monotherapy or in combination with other anticancer therapies for better clinical outcomes. Here, we review recent advances, current challenges, and prospects of bacteria and bacterial products in the development of BBCTs.
Highlights
Various bacterial species have proven useful in harnessing antitumoral immunity by initiating innate and adaptive immune responses in pre-clinical and clinical studies, which has increased the chances of tumor elimination without additional secondary side effects [10–12]
We review recent advances in bacterial-mediated drug and delivery systems’ discovery and discuss the benefits and current challenges in these serving as anti-cancer treatments
Gene transfer occurs when attenuated bacteria release plasmid DNA into the cytoplasm of the host cells, which culminates in the expression of the transfected genes at the cellular level [57]. This can be further targeted for silencing of genes that favor tumor growth through the use of RNA interference. This entails the transfer of small hairpin RNAs encoded into a plasmid, which are transfected in the cytoplasm into small interfering RNAs, and act to promote degradation of target mRNA in tumors
Summary
Bacteria have been of particular interest due to their natural motile ability, which allows them to move away from the vasculature and penetrate hypoxic regions of the tumor [4] and subsequently proliferate within tumor cells [5]. This solves the problem commonly faced by chemotherapeutics where they reach mainly the vascularized outside edges of the tumor but not the hypoxic core. Direct delivery of drugs via bacteria to the tumor site enhances specific cancer-targeting therapies and limits the negative effects of treatment [7]. Bacteria can be harnessed to produce drugs within tumor cells, essentially manufacturing therapeutic molecules on site [8].
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