Abstract
Cancer is the world's second leading cause of death in humans. Conventional anticancer therapies are often associated with lack of tumor specificity, failure to detect small metastases, increased resistance of tumors to anticancer drugs, and unintended adverse effects. Numerous alternative and better strategies in cancer treatment have been developed to overcome the negative effects of traditional cancer therapies. More than a century ago, William Coley, the father of cancer immounotherapy, laid the groundwork for bacterial anticancer therapy. Bacterial immunotherapy has been emerging as a potential anticancer therapy. Moreover, certain obligate and facultative anaerobic bacterial species are exploited as vectors for gene delivery to treat cancer. These genes encode for anticancer agents, cytokines, cytotoxic peptides, anti-angiogenic proteins, therapeutic molecules and prodrug-converting enzymes. Genetically engineered bacterial strains of Salmonella, Bifidobacterium, Clostridium and Listeria are widely used to deliver genes in anticancer therapy since they can selectively accumulate in solid tumors with a hypoxic/necrotic core in vivo, providing appealing delivery systems to target therapeutic agents and immunomodulatory molecules to the site of tumor. Certain genetically modified bacterial species such as Bifidobacterium longum and Bacillus licheniformis have been effectively used for the enzyme/prodrug therapy for cancer. Furthermore, certain anaerobic bacteria are emerging as potential tumor markers due to the increased mobility and the selectivity in germinating and multiplying in hypoxic/anoxic environments. Many of these novel developments have been studied extensively in different experimental models of cancer and certain clinical trials are ongoing for some treatment modalities. Although favourable results have shown so far, further studies and technological innovations are required to ensure the efficacy of bacterial anticancer therapy.
Highlights
Cancer is one of the major causes of human death worldwide and according to the World Health Organization (WHO), the burden of cancer is increasing at an alarming rate globally [1]
Scientists revealed that certain obligate and facultative anaerobic bacterial species such as Clostridium thrive only in hypoxic/anoxic neoplastic tissues, whereas they lose their viability in the well-oxygenated areas, suggesting that they are innocuous to the remaining healthy tissues of the body [11]
This remarkable eradication was due to direct killing by Listeria monocytogenes and by cytotoxic T lymphocytes (CTL) responses against Listeria monocytogenes antigens, including the truncated listeriolysin O (LLO).This LMbased vaccine has been successfully used in eliminating metastatic breast cancers [47]
Summary
Cancer is one of the major causes of human death worldwide and according to the World Health Organization (WHO), the burden of cancer is increasing at an alarming rate globally [1]. Uncontrollable division of abnormal cells is known as cancer and these cancerous cells often invade adjoining. There are over 200 different types of known cancers which affect human beings. Benign tumors are less harmful and not considered as malignant tumors. They are often treatable when compared to malignant cancers, which are highly dangerous, debilitating and life-threatening. A significant proportion of cancers can be cured, by conventional therapies such as surgery, radiotherapy or chemotherapy, especially if they are detected early. A number of novel therapeutic strategies have been developed as potential anti-cancer therapies to overcome these adverse effects of conventional anti-cancer therapies. Bacterial anti-cancer therapy is an emerging novel approach in cancer treatment [2, 3]
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