Bugs as Drugs: Neglected but a Promising Future Therapeutic Strategy in Cancer

Abstract

Effective cancer treatment is an urgent need due to the rising incidence of cancer. One of the most promising future strategies in cancer treatment is using microorganisms as cancer indicators, prophylactic agents, immune activators, vaccines or vectors in antitumor therapy. The success of bacteria-mediated chemotherapy will be dependent on the balance of therapeutic benefit and the control of bacterial infection in the body. Additionally, protozoans and viruses have the potential to be used in cancer therapy. This review summarizes how these microorganisms interact with tumor microenvironments and the challenges of a ‘bugs as drugs' approach in cancer therapy. Several standpoints are discussed, such as bacteria as vectors for gene therapy that shuttle therapeutic compounds into tumor tissues, their intrinsic antitumor activities and their combination with chemotherapy or radiotherapy. Bug-based cancer therapy is a two-edged sword and we need to find the opportunities by overcoming the challenges.

Bacterial Therapy of Cancer: A Way to the Dustbin of History or to the Medicine of the Future?

“…Today, much more is known about the possible ways in which bacteria can affect the development of tumors [67][68][69]. Currently, one of the main and generally accepted versions of the beneficial effect of bacterial therapeutic anticancer "vaccines" is the version stimulating the patient s immune system to fight the disease [70,71]. The entry of microorganisms into the human body leads to the activation of immune mechanisms, which is manifested in increasing the number and recruitment of innate immune cells (especially neutrophils, monocytes/macrophages, and NK cells), the activation of cells of acquired immunity-that is, T and B lymphocytes-and the increased production of proinflammatory cytokines [72].…”

Bacteria in the cancer therapy

“…Bacteria can become a vehicle for delivering anti-cancer agents, cytotoxic peptides, therapeutic proteins or prodrug converting enzymes to tumors. Two studies have described the production of Cytolysin A(ClyA), a pore-forming hemolytic protein in E.coli K-12 and S.typhimurium [10,11]. In the model of CT26 mice, this strategy can effectively kill hypoxia regions of tumors that resist radiotherapy.…”

Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery

“…As a result, it is critical that antitumoral therapy explicitly targets the deeper and hypoxic regions of the tumor for optimum treatment. Due to bacteria's self-propulsion and guidance capabilities, bacteria-mediated tumor therapy (BMTT) allows for successful intratumoral targeting [ 213 ]. It is possible for them to actively swim away from the tumor vasculature and reach more favorable settings for bacteria growth in deeper locations.…”