Статті в журналах: "Bacteria in cancer therapy"

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Duong, Mai Thi-Quynh, Yeshan Qin, Sung-Hwan You, and Jung-Joon Min. "Bacteria-cancer interactions: bacteria-based cancer therapy." Experimental & Molecular Medicine 51, no. 12 (December 2019): 1–15. http://dx.doi.org/10.1038/s12276-019-0297-0.

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AbstractRecent 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.

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Yaghoubi, Atieh, Majid Khazaei, Seyed Mahdi Hasanian, Amir Avan, William C. Cho, and Saman Soleimanpour. "Bacteriotherapy in Breast Cancer." International Journal of Molecular Sciences 20, no. 23 (November 23, 2019): 5880. http://dx.doi.org/10.3390/ijms20235880.

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Breast cancer is the second most common cause of cancer-related mortality among women around the world. Conventional treatments in the fight against breast cancer, such as chemotherapy, are being challenged regarding their effectiveness. Thus, strategies for the treatment of breast cancer need to be continuously refined to achieve a better patient outcome. We know that a number of bacteria are pathogenic and some are even associated with tumor development, however, recent studies have demonstrated interesting results suggesting some bacteria may have potential for cancer therapy. Therefore, the therapeutic role of bacteria has aroused attention in medical and pharmaceutical studies. Furthermore, genetic engineering has been used in bacterial therapy and may led to greater efficacy with few side effects. Some genetically modified non-pathogenic bacterial species are more successful due to their selectivity for cancer cells but with low toxicity for normal cells. Some live, attenuated, or genetically modified bacterias are capable to multiply in tumors and inhibit their growth. This article aims to review the role of bacteria and their products including bacterial peptides, bacteriocins, and toxins for the treatment of breast cancer.

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Harimoto, Tetsuhiro, and Tal Danino. "Engineering bacteria for cancer therapy." Emerging Topics in Life Sciences 3, no. 5 (October 11, 2019): 623–29. http://dx.doi.org/10.1042/etls20190096.

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The engineering of living cells and microbes is ushering in a new era of cancer therapy. Due to recent microbiome studies indicating the prevalence of bacteria within the human body and specifically in tumor tissue, bacteria have generated significant interest as potential targets for cancer therapy. Notably, a multitude of empirical studies over the past decades have demonstrated that administered bacteria home and grow in tumors due to reduced immune surveillance of tumor necrotic cores. Given their specificity for tumors, bacteria present a unique opportunity to be engineered as intelligent delivery vehicles for cancer therapy with synthetic biology techniques. In this review, we discuss the history, current state, and future challenges associated with using bacteria as a cancer therapy.

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Mathuriya, Abhilasha S. "Magnetotactic bacteria for cancer therapy." Biotechnology Letters 37, no. 3 (November 12, 2014): 491–98. http://dx.doi.org/10.1007/s10529-014-1728-6.

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Dougan, Michael, and Stephanie K. Dougan. "Programmable bacteria as cancer therapy." Nature Medicine 25, no. 7 (July 2019): 1030–31. http://dx.doi.org/10.1038/s41591-019-0513-4.

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Fdez-Gubieda, M. L., J. Alonso, A. García-Prieto, A. García-Arribas, L. Fernández Barquín, and A. Muela. "Magnetotactic bacteria for cancer therapy." Journal of Applied Physics 128, no. 7 (August 21, 2020): 070902. http://dx.doi.org/10.1063/5.0018036.

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Darmov, I. V., Ya A. Kibirev, I. V. Marakulin, and S. N. Yanov. "USE OF BACTERIA IN CANCER THERAPY (REVIEW)." Russian Journal of Biotherapy 18, no. 4 (December 2, 2019): 34–42. http://dx.doi.org/10.17650/1726-9784-2019-18-4-34-42.

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Bacterial drugs for the treatment of malignant tumors have been discovered more than a hundred years ago, but their use in clinical practice has been very limited. In the past decade, there has been a revival of interest in the development of bacterial-based cancer biotherapies, which is associated with advances in genetic engineering and in depth knowledge of the mechanisms of the infectious process and immunity. The purpose of this review is to examine the current state and prospects for the development and use of drugs based on live bacterium, intended for the treatment of malignant tumors. The review presents evaluation data on experimental models of the antitumor potential of various species and strains of bacteria; the most significant results of clinical trials of bacterial antitumor agents; current trends in the design of bacterial strains for targeted drug delivery to the tumor. It is concluded that development of bacterial drugs for cancer therapy is a perspective branch of experimental oncology.

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Yoon, Wonsuck, Yongsung Park, Seunghyun Kim, Yongkeun Park, and Chul Yong Kim. "Combined Therapy with microRNA-Expressing Salmonella and Irradiation in Melanoma." Microorganisms 9, no. 11 (November 22, 2021): 2408. http://dx.doi.org/10.3390/microorganisms9112408.

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Anticancer treatment strategies using bacteria as a vector are currently expanding with the development of anticancer drugs. Here, we present a research strategy to develop anticancer drugs using bacteria that contain miRNAs. We also present a strategy for the development of novel bacterial anticancer drugs in combination with radiation. Salmonella strains expressing miRNA were produced by modifying the miRNA expression vector encoding INHA, a radiation-resistant gene developed previously. The anticancer effect of INHA was confirmed using skin cancer cell lines. We also tested a combination strategy comprising bacteria and radiation for its anticancer efficacy against radiation-resistant mouse melanoma to increase the efficacy of radiation therapy as a novel strategy. The recombinant strain was confirmed to promote effective cell death even when combined with radiation therapy, which exerts its cytotoxicity by enhancing reactive oxygen species production. Moreover, a combination of bacterial and radiation therapy enhanced radiotherapy efficacy. When combined with radiation therapy, bacterial therapy exhibited effective anti-cancer properties even when administered to animals harboring radiation-resistant tumors. This strategy may promote the secretion of cytokines in cells and more effectively reduce the number of bacteria remaining in the animal. Thus, this study may lead to the development of a strategy to improve the effectiveness of radiation therapy using Salmonella expressing cancer-specific miRNA for intractable cancers such as those resistant to radiation.

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Gupta, Kajal H., Christina Nowicki, Eileena F. Giurini, Amanda L. Marzo, and Andrew Zloza. "Bacterial-Based Cancer Therapy (BBCT): Recent Advances, Current Challenges, and Future Prospects for Cancer Immunotherapy." Vaccines 9, no. 12 (December 18, 2021): 1497. http://dx.doi.org/10.3390/vaccines9121497.

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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.

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Yoo, Su Woong, Dinh-huy Nguyen, Suhyeon Park, Hyeri Lee, Chang-Moon Lee, Changho Lee, and Jung-Joon Min. "Development of Dual-Scale Fluorescence Endoscopy for In Vivo Bacteria Imaging in an Orthotopic Mouse Colon Tumor Model." Applied Sciences 10, no. 3 (January 24, 2020): 844. http://dx.doi.org/10.3390/app10030844.

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Colorectal cancer is a representative cancer where early diagnosis and proper treatment monitoring are important. Recently, cancer treatment using bacteria has actively progressed and has been successfully monitored using fluorescence imaging techniques. However, because subcutaneous tumor models are limited in reflecting the actual colorectal cancer situation, new imaging approaches are needed to observe cancers growing in the colon. The fluorescence endoscopic approach is an optimal monitoring modality to evaluate the therapeutic response of bacteria in orthotopic colon cancer. In this study, we developed dual-scaled fluorescence endoscopy (DSFE) by combining wide-field fluorescence endoscopy (WFE) and confocal fluorescence endomicroscopy (CFEM) and demonstrated its usefulness for evaluating bacterial therapy. Firstly, the endoscopic probe of DSFE was developed by integrating the CFEM probe into the guide sheath of WFE. Secondly, colorectal cancer tumor growth and tumors infiltrating the fluorescent bacteria were successfully monitored at the multi-scale using DSFE. Finally, the bacterial distribution of the tumor and organs were imaged and quantitatively analyzed using CFEM. DSFE successfully exhibited fluorescent bacterial signals in an orthotopic mouse colon tumor model. Thus, it can be concluded that the DSFE system is a promising modality to monitor bacterial therapy in vivo.

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Cao, Zhenping, and Jinyao Liu. "Bacteria and bacterial derivatives as drug carriers for cancer therapy." Journal of Controlled Release 326 (October 2020): 396–407. http://dx.doi.org/10.1016/j.jconrel.2020.07.009.

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Torres, Wheeler, Víctor Lameda, Luis Carlos Olivar, Carla Navarro, Jorge Fuenmayor, Adrián Pérez, Andres Mindiola, et al. "Bacteria in cancer therapy: beyond immunostimulation." Journal of Cancer Metastasis and Treatment 4, no. 1 (January 24, 2018): 4. http://dx.doi.org/10.20517/2394-4722.2017.49.

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Patel, A. G., and S. H. Kaufmann. "Targeting Bacteria to Improve Cancer Therapy." Science 330, no. 6005 (November 4, 2010): 766–67. http://dx.doi.org/10.1126/science.1198310.

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Rong, Lei, Qi Lei, and Xian-Zheng Zhang. "Engineering Living Bacteria for Cancer Therapy." ACS Applied Bio Materials 3, no. 12 (November 18, 2020): 8136–45. http://dx.doi.org/10.1021/acsabm.0c01286.

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Ali, Md Kaisar, Qing Liu, Kang Liang, Pei Li, and Qingke Kong. "Bacteria-derived minicells for cancer therapy." Cancer Letters 491 (October 2020): 11–21. http://dx.doi.org/10.1016/j.canlet.2020.07.024.

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Trivanović, Dragan, Krešimir Pavelić, and Željka Peršurić. "Fighting Cancer with Bacteria and Their Toxins." International Journal of Molecular Sciences 22, no. 23 (November 30, 2021): 12980. http://dx.doi.org/10.3390/ijms222312980.

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Cancer is one of the most important global health problems that continues to demand new treatment strategies. Many bacteria that cause persistent infections play a role in carcinogenesis. However, since bacteria are well studied in terms of molecular mechanisms, they have been proposed as an interesting solution to treat cancer. In this review, we present the use of bacteria, and particularly bacterial toxins, in cancer therapy, highlighting the advantages and limitations of bacterial toxins. Proteomics, as one of the omics disciplines, is essential for the study of bacterial toxins. Advances in proteomics have contributed to better characterization of bacterial toxins, but also to the development of anticancer drugs based on bacterial toxins. In addition, we highlight the current state of knowledge in the rapidly developing field of bacterial extracellular vesicles, with a focus on their recent application as immunotherapeutic agents.

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Farashi-Bonab, Samad, and Nemat Khansari. "Salmonella-based Anticancer Vaccines and their Efficacy." Vaccination Research – Open Journal 4, no. 1 (December 31, 2019): 5–11. http://dx.doi.org/10.17140/vroj-4-111.

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Surgery, chemotherapy, and radiotherapy are successfully used to treat patients with tumors or cancers. However, the innovation of more potent therapeutic modalities is essential for the efficient treatment of patients with advanced cancers. More than two centuries ago, bacteria have been observed to have beneficial effects in some cancer patients. Virulence factors of some bacteria and their infectious behavior in the body suggest their effectiveness in tumor suppression. At present, bacillus calmette-guérin (BCG), a live attenuated strain of Mycobacterium bovis, is currently used to treat bladder cancer. Some other bacteria have also been found to have antitumor activities. Anaerobic bacteria can colonize solid tumors and exert an intrinsic antitumor effect. Salmonella is the most studied bacterium in the field of bacterial anticancer therapy in preclinical studies. In this article, we discuss progress in the development of bacterial anticancer vaccines, especially Salmonella-based vaccines, their antitumor efficacy, and mechanisms involved in vaccine-mediated cancer cell death.

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Decker, Amanda R., Tetsuhiro Harimoto, Steve A. Sastra, Tal Danino, and Kenneth Olive. "Abstract B028: Bacterial cytotoxin therapy limits tumor growth for pancreatic ductal adenocarcinoma." Cancer Research 82, no. 22_Supplement (November 15, 2022): B028. http://dx.doi.org/10.1158/1538-7445.panca22-b028.

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Abstract Treating pancreatic ductal adenocarcinoma (PDAC) with systemic chemotherapeutic drugs has remained a challenge, due in part to the hypovascularized and poorly perfused nature of PDAC tumors, impeding the accumulation of systemically delivered drugs. Several clinical trials aimed at improving drug delivery in PDAC, through targeting of ECM components (HALO-301) or stromal angiogenic signaling (IPI-926-03) have unfortunately not been effective. However, the features that have interfered with systemic therapy in PDAC are potential advantages for the use of bacterial therapies, as bacteria can actively migrate through tissues, thrive in hypoxic microenvironments, and benefit from local immune suppression. Recent developments in the field of synthetic biology have made it possible to engineer complex logic circuits into bacteria, enabling the production of anticancer therapies directly within the tumor parenchyma. Furthermore, live bacteria, once colonized within the tumor niche, are capable of providing a stable source of anticancer compounds directly, rather than relying on repeated systemic doses. We have therefore worked to develop novel bacterial strains and demonstrate preclinical efficacy of a novel strain of therapeutic bacteria for targeting PDAC. We began by testing a range of bacteria-produced toxins and identified the pore-forming protein theta toxin as having the greatest effect in both 2D cell culture and PDAC explant (tissue slice) models. We then engineered a non-toxic probiotic bacteria, E. coli Nissle 1917, to produce either theta toxin or GFP following induction with acyl-homoserine lactone (AHL). To assess preclinical efficacy, we performed intratumoral injections of live GFP- and theta-expressing bacteria into the “KPC” genetically engineered mouse model (Kras LSL.G12D/+; Tp53 LSL.R172H/+; PdxCre tg/+). While GFP-producing bacteria did not induce a change in tumor growth kinetics, treatment with theta toxin-producing bacteria demonstrated prolonged stabilization of tumor growth, increasing the doubling time from 13.7 days (GFP) to 32.5 days (theta) without additional therapy. Indeed, one theta-treated KPC animal lived 113 days following a single bacterial injection, compared to a median of ~12 days for vehicle- or gemcitabine-treated historical controls. Histological analyses demonstrated that diffuse populations of bacteria co-localized with regions of tumor necrosis and cell death, but that bacterial presence and evidence of increased cell death was not observed in healthy tissues, such as the lung, liver, intestine, and diaphragm. Strikingly, while there was minimal spread of bacteria to non-tumor tissues, we observed translocation of the bacteria to regions of liver metastases and distant papillomas following injection of the primary pancreatic tumor, suggesting a mechanism for targeting both known and unknown metastases following local administration. Together these studies demonstrate potent preclinical activity of cytotoxic bacterial therapy as a novel strategy to circumvent the challenges of systemic treatment of PDAC. Citation Format: Amanda R. Decker, Tetsuhiro Harimoto, Steve A. Sastra, Tal Danino, Kenneth Olive. Bacterial cytotoxin therapy limits tumor growth for pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B028.

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Gardlik, R., M. Behuliak, R. Palffy, P. Celec, and C. J. Li. "Gene therapy for cancer: bacteria-mediated anti-angiogenesis therapy." Gene Therapy 18, no. 5 (January 13, 2011): 425–31. http://dx.doi.org/10.1038/gt.2010.176.

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Yin, Ting, Zhenying Diao, Nicholas Thomas Blum, Long Qiu, Aiqing Ma, and Peng Huang. "Engineering Bacteria and Bionic Bacterial Derivatives with Nanoparticles for Cancer Therapy." Small 18, no. 12 (December 15, 2021): 2104643. http://dx.doi.org/10.1002/smll.202104643.

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Yusuf, Kafayat, Venkatesh Sampath, and Shahid Umar. "Bacterial Infections and Cancer: Exploring This Association And Its Implications for Cancer Patients." International Journal of Molecular Sciences 24, no. 4 (February 4, 2023): 3110. http://dx.doi.org/10.3390/ijms24043110.

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Bacterial infections are common in the etiology of human diseases owing to the ubiquity of bacteria. Such infections promote the development of periodontal disease, bacterial pneumonia, typhoid, acute gastroenteritis, and diarrhea in susceptible hosts. These diseases may be resolved using antibiotics/antimicrobial therapy in some hosts. However, other hosts may be unable to eliminate the bacteria, allowing them to persist for long durations and significantly increasing the carrier's risk of developing cancer over time. Indeed, infectious pathogens are modifiable cancer risk factors, and through this comprehensive review, we highlight the complex relationship between bacterial infections and the development of several cancer types. For this review, searches were performed on the PubMed, Embase, and Web of Science databases encompassing the entirety of 2022. Based on our investigation, we found several critical associations, of which some are causative: Porphyromonas gingivalis and Fusobacterium nucleatum are associated with periodontal disease, Salmonella spp., Clostridium perfringens, Escherichia coli, Campylobacter spp., and Shigella are associated with gastroenteritis. Helicobacter pylori infection is implicated in the etiology of gastric cancer, and persistent Chlamydia infections present a risk factor for the development of cervical carcinoma, especially in patients with the human papillomavirus (HPV) coinfection. Salmonella typhi infections are linked with gallbladder cancer, and Chlamydia pneumoniae infection is implicated in lung cancer, etc. This knowledge helps identify the adaptation strategies used by bacteria to evade antibiotic/antimicrobial therapy. The article also sheds light on the role of antibiotics in cancer treatment, the consequences of their use, and strategies for limiting antibiotic resistance. Finally, the dual role of bacteria in cancer development as well as in cancer therapy is briefly discussed, as this is an area that may help to facilitate the development of novel microbe-based therapeutics as a means of securing improved outcomes.

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Mills, Hilla, Ronald Acquah, Nova Tang, Luke Cheung, Susanne Klenk, Ronald Glassen, Magali Pirson, Alain Albert, Duong Trinh Hoang, and Thang Nguyen Van. "The Use of Bacteria in Cancer Treatment: A Review from the Perspective of Cellular Microbiology." Emergency Medicine International 2022 (August 8, 2022): 1–6. http://dx.doi.org/10.1155/2022/8127137.

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Cellular microbiology, which is the interaction between harmful microbes and infected cells, is important in the determination of the bacterial infection processes and in the progression of data of different cellular mechanisms. The therapeutic role of bacteria has gained attention since the known methods such as radiation, chemotherapy, and immunotherapy have got drawbacks. Bacteria have demonstrated a favorable impact in treating cancer through eradication of tumors. Bacteria, in cancer treatment, have proven to be promising and have been shown in some of the previous work that it can successfully suppress the growth of tumors. In this paper, we analyzed the difficulties and settlement for using bacteria in cancer therapy as well the mechanisms in which bacteria works in order to achieve tumor eradication. Future works may focus on the use of bacteria along with other treatments in order to achieve effective tumor therapy.

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Sawant, Shruti S., Suyash M. Patil, Vivek Gupta, and Nitesh K. Kunda. "Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment." International Journal of Molecular Sciences 21, no. 20 (October 14, 2020): 7575. http://dx.doi.org/10.3390/ijms21207575.

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Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.

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Divyashree, Mithoor, Shama K. Prakash, Vankadari Aditya, Alaa AA Aljabali, Khalid J. Alzahrani, Vasco Azevedo, Aristóteles Góes-Neto, Murtaza M. Tambuwala, and Debmalya Barh. "Bugs as drugs: neglected but a promising future therapeutic strategy in cancer." Future Oncology 18, no. 13 (April 2022): 1609–26. http://dx.doi.org/10.2217/fon-2021-1137.

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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.

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Wang, Cheng-Zhi, Robert A. Kazmierczak, and Abraham Eisenstark. "Strains, Mechanism, and Perspective:Salmonella-Based Cancer Therapy." International Journal of Microbiology 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/5678702.

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Recently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such asSalmonella,Listeria,Escherichia, andClostridiumhave proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents. Synthetic biology techniques have also driven the development of new bacterial-based cancer therapies. However, basic questions about the mechanisms of bacterial-mediated tumor targeting and destruction are still being elucidated. In this review, we focus on three tumor-therapeuticSalmonellamodels, the most intensively studied bacterial genus in this field. One of theseSalmonellamodels is ourSalmonella entericaserovar Typhimurium LT2 derived strain CRC2631, engineered to minimize toxicity but maximize tumor-targeting and destruction effects. The other two are VNP20009 and A1-R. We compare the means by which these therapeutic candidate strain models were selected for study, their tumor targeting and tumor destruction phenotypesin vitroandin vivo, and what is currently known about the mechanisms by which they target and destroy tumors.

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Mueller, Anna-Lena, Aranka Brockmueller, Niusha Fahimi, Tahere Ghotbi, Sara Hashemi, Sadaf Sadri, Negar Khorshidi, Ajaikumar B. Kunnumakkara, and Mehdi Shakibaei. "Bacteria-Mediated Modulatory Strategies for Colorectal Cancer Treatment." Biomedicines 10, no. 4 (April 1, 2022): 832. http://dx.doi.org/10.3390/biomedicines10040832.

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Colorectal cancer (CRC) is one of the most common tumors worldwide, with a higher rate of distant metastases than other malignancies and with regular occurrence of drug resistance. Therefore, scientists are forced to further develop novel and innovative therapeutic treatment strategies, whereby it has been discovered microorganisms, albeit linked to CRC pathogenesis, are able to act as highly selective CRC treatment agents. Consequently, researchers are increasingly focusing on bacteriotherapy as a novel therapeutic strategy with less or no side effects compared to standard cancer treatment methods. With multiple successful trials making use of various bacteria-associated mechanisms, bacteriotherapy in cancer treatment is on its way to become a promising tool in CRC targeting therapy. In this study, we describe the anti-cancer effects of bacterial therapy focusing on the treatment of CRC as well as diverse modulatory mechanisms and techniques that bacteriotherapy offers such as bacterial-related biotherapeutics including peptides, toxins, bacteriocins or the use of bacterial carriers and underlying molecular processes to target colorectal tumors.

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Decker, Amanda R., Tetsuhiro Harimoto, Steve A. Sastra, Tal Danino, and Kenneth P. Olive. "Abstract PO-033: Bacterial cytotoxin therapy limits tumor growth for pancreatic ductal adenocarcinoma." Cancer Research 81, no. 22_Supplement (November 15, 2021): PO—033—PO—033. http://dx.doi.org/10.1158/1538-7445.panca21-po-033.

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Abstract Treating pancreatic ductal adenocarcinoma (PDAC) with systemic chemotherapeutic drugs has remained a challenge, due in part to the hypovascularized and poorly perfused nature of PDAC tumors. Limited blood flow within the tumor tissue creates an extremely hypoxic microenvironment and impedes the accumulation of drugs. Moreover, local immunosuppression in PDAC has so far limited the efficacy of immunotherapy approaches. However, these very features that have interfered with systemic therapy in PDAC (hypoperfusion, hypoxia, and immunosuppression) are potential advantages for the use of bacterial therapies. Bacteria have been used as a directed cancer therapy for over 100 years, starting with Dr. William Coley’s use of heat killed bacteria (Coley’s Toxin) against sarcomas in 1893. Recent developments in the field of synthetic biology have made it possible to engineer complex logical circuits into bacteria, enabling the manufacture of anticancer therapies directly within the tumor parenchyma. Bacteria can actively migrate through tissues, they can thrive in hypoxic microenvironments, and they benefit from the local immune suppression. We have therefore worked to develop novel bacterial strains for targeting PDAC. We began by testing a range of bacteria-derived toxins that could be used as a payload to target PDAC. These toxins were produced by an engineered strain of a non-toxic, probiotic E. coli Nissle 1917. We identified four pore-forming toxins that significantly reduced viability of the cells compared to bacterially produced GFP: hemolysin E, heat stable enterotoxin, magainin, and theta toxin. We then performed a secondary screen using a novel PDAC explant model system developed in our lab, in which thick slices of murine or human PDAC are culture intact for up to 7 days. Consistent with the monolayer screen, two of the candidate compounds, heat stable enterotoxin and theta toxin, significantly increased tissue death compared to non-toxic GFP-producing bacteria. Finally, we delivered live bacteria producing either toxins or GFP into KPC mouse tumors through intratumoral injection. While GFP-producing strains did not induce a change in tumor growth kinetics, theta toxin treatment demonstrated an immediate, prolonged stabilization of tumor volume for more than a month. Histological analyses of treated tumors demonstrated that diffuse populations of bacteria co-localized with regions of tumor necrosis and cell death. Most interestingly, while there was minimal spread of bacteria to healthy non-target tissues, translocation of the bacteria did occur to regions of liver metastases and secondary papilloma tumors, suggesting a mechanism for diffuse treatment of known and unknown metastases following the initial treatment of the primary tumor. Together these studies demonstrate that cytotoxic bacterial therapy is an effective candidate strategy to circumvent the difficulties in systemic treatment of PDAC. Citation Format: Amanda R. Decker, Tetsuhiro Harimoto, Steve A. Sastra, Tal Danino, Kenneth P. Olive. Bacterial cytotoxin therapy limits tumor growth for pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-033.

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Tajamal, Mamoon, Ambreen Qasim, Qasim Javed, Marium Abdul Majeed, Saba Imtiaz, Mehwish Mehwish, Taiyyibah Basharat, Shumaila Yousaf, and Rasab Javed. "Recent Advances in Bacterial and Viral Genomics for Cancer Therapy." Haya: The Saudi Journal of Life Sciences 7, no. 10 (October 29, 2022): 294–98. http://dx.doi.org/10.36348/sjls.2020.v07i10.004.

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Bacterial and viral therapies have gained enough success and attention for biological cancer treatments. There is a need to protect the living tissues of the body that are helpful for activating the immune responses. Many failures are associated with the conservational therapies that render them for the current era of medical sciences. Viral and bacterial genomes have been used for targeting the initial basis of metastasis and inhibiting the growth of cancerous cells. S. pyogenes OK-432 strain showed action against cancerous cells with intact bindings to the proliferative tissues. Phenazine 1-carboxylic acids have anticancer nature and pose a high level of cytotoxicity against the. Salmonella strain (KST0650) showed maximum potential against CT26 cancer cells. Oncolytic biologically and virologically group of the controlled viruses that have been used for tumor treatment. Some critical cancers under medications such as hormone therapy- induced helpful for prolonged life span. Pro-active drugs and combinations of probiotics also prevent the bacteria from synthesizing the protective layer of peptidoglycan.

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McCulloch, John A., and Giorgio Trinchieri. "Gut bacteria enable prostate cancer growth." Science 374, no. 6564 (October 8, 2021): 154–55. http://dx.doi.org/10.1126/science.abl7070.

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30

Yang, Meiyang, Fuwei Yang, Weijun Chen, Shenhuan Liu, Lipeng Qiu, and Jinghua Chen. "Bacteria-mediated cancer therapies: opportunities and challenges." Biomaterials Science 9, no. 17 (2021): 5732–44. http://dx.doi.org/10.1039/d1bm00634g.

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Advances of engineered bacteria will promote tumor therapy into the era of precision medicine. Introducing synthetic biology, nanotechnology and synergistic treatment into bacteria-mediated cancer therapy enhances its safety and efficacy.

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31

Seely, Kevin D., Amanda D. Morgan, Lauren D. Hagenstein, Garrett M. Florey, and James M. Small. "Bacterial Involvement in Progression and Metastasis of Colorectal Neoplasia." Cancers 14, no. 4 (February 17, 2022): 1019. http://dx.doi.org/10.3390/cancers14041019.

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While the gut microbiome is composed of numerous bacteria, specific bacteria within the gut may play a significant role in carcinogenesis, progression, and metastasis of colorectal carcinoma (CRC). Certain microbial species are known to be associated with specific cancers; however, the interrelationship between bacteria and metastasis is still enigmatic. Mounting evidence suggests that bacteria participate in cancer organotropism during solid tumor metastasis. A critical review of the literature was conducted to better characterize what is known about bacteria populating a distant site and whether a tumor depends upon the same microenvironment during or after metastasis. The processes of carcinogenesis, tumor growth and metastatic spread in the setting of bacterial infection were examined in detail. The literature was scrutinized to discover the role of the lymphatic and venous systems in tumor metastasis and how microbes affect these processes. Some bacteria have a potent ability to enhance epithelial–mesenchymal transition, a critical step in the metastatic cascade. Bacteria also can modify the microenvironment and the local immune profile at a metastatic site. Early targeted antibiotic therapy should be further investigated as a measure to prevent metastatic spread in the setting of bacterial infection.

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32

Sen, Preenu P., Gautham A, Murugan Manavalan, and Mansoor Ani Najeeb. "BACTERIA IN CANCER THERAPY: AN EMERGING ROBUST STRATEGY." International Research Journal of Pharmacy 4, no. 5 (May 28, 2013): 1–4. http://dx.doi.org/10.7897/2230-8407.04501.

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Cheng, C.-M., Y.-L. Lu, K.-H. Chuang, W.-C. Hung, J. Shiea, Y.-C. Su, C.-H. Kao, B.-M. Chen, S. Roffler, and T.-L. Cheng. "Tumor-targeting prodrug-activating bacteria for cancer therapy." Cancer Gene Therapy 15, no. 6 (March 28, 2008): 393–401. http://dx.doi.org/10.1038/cgt.2008.10.

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Patyar, S., R. Joshi, DS Prasad Byrav, A. Prakash, B. Medhi, and BK Das. "Bacteria in cancer therapy: a novel experimental strategy." Journal of Biomedical Science 17, no. 1 (2010): 21. http://dx.doi.org/10.1186/1423-0127-17-21.

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Baban, Chwanrow K., Michelle Cronin, Deirdre O’Hanlon, Gerald C. O’Sullivan, and Mark Tangney. "Bacteria as vectors for gene therapy of cancer." Bioengineered Bugs 1, no. 6 (November 2010): 385–94. http://dx.doi.org/10.4161/bbug.1.6.13146.

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Al-Saafeen, Besan H., Maria J. Fernandez-Cabezudo, and Basel K. al-Ramadi. "Integration of Salmonella into Combination Cancer Therapy." Cancers 13, no. 13 (June 28, 2021): 3228. http://dx.doi.org/10.3390/cancers13133228.

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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.

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Jiménez-Jiménez, Carla, Víctor M. Moreno, and María Vallet-Regí. "Bacteria-Assisted Transport of Nanomaterials to Improve Drug Delivery in Cancer Therapy." Nanomaterials 12, no. 2 (January 17, 2022): 288. http://dx.doi.org/10.3390/nano12020288.

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Currently, the design of nanomaterials for the treatment of different pathologies is presenting a major impact on biomedical research. Thanks to this, nanoparticles represent a successful strategy for the delivery of high amounts of drugs for the treatment of cancer. Different nanosystems have been designed to combat this pathology. However, the poor penetration of these nanomaterials into the tumor tissue prevents the drug from entering the inner regions of the tumor. Some bacterial strains have self-propulsion and guiding capacity thanks to their flagella. They also have a preference to accumulate in certain tumor regions due to the presence of different chemo-attractants factors. Bioconjugation reactions allow the binding of nanoparticles in living systems, such as cells or bacteria, in a simple way. Therefore, bacteria are being used as a transport vehicle for nanoparticles, facilitating their penetration and the subsequent release of the drug inside the tumor. This review would summarize the literature on the anchoring methods of diverse nanosystems in bacteria and, interestingly, their advantages and possible applications in cancer therapy.

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Yi, Xuan, Hailin Zhou, Yu Chao, Saisai Xiong, Jing Zhong, Zhifang Chai, Kai Yang, and Zhuang Liu. "Bacteria-triggered tumor-specific thrombosis to enable potent photothermal immunotherapy of cancer." Science Advances 6, no. 33 (August 2020): eaba3546. http://dx.doi.org/10.1126/sciadv.aba3546.

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We discovered that attenuated Salmonella after intravenous injection would proliferate within various types of solid tumors but show rapid clearance in normal organs, without rendering notable toxicity. Bacteria-induced inflammation would trigger thrombosis in the infected tumors by destroying tumor blood vessels. Six types of tested tumors would all turn into darkened color with strong near-infrared absorbance, as observed by photoacoustic imaging. Under laser irradiation, those bacterial-infected tumors would be effectively ablated. Because of the immune-stimulation function, such bacteria-based photothermal therapy (PTT) would subsequently trigger antitumor immune responses, which could be further enhanced by immune checkpoint blockade to effectively suppress the growth of abscopal tumors. A robust immune memory effect to reject rechallenged tumors is also observed after bacteria-based PTT. Our work demonstrates that bacteria by themselves could act as a tumor-specific PTT agent to enable photoimmunotherapy cancer therapy to inhibit tumor metastasis and recurrence.

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Felgner, Sebastian, Dino Kocijancic, Michael Frahm, and Siegfried Weiss. "Bacteria in Cancer Therapy: Renaissance of an Old Concept." International Journal of Microbiology 2016 (2016): 1–14. http://dx.doi.org/10.1155/2016/8451728.

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The rising incidence of cancer cases worldwide generates an urgent need of novel treatment options. Applying bacteria may represent a valuable therapeutic variant that is intensively investigated nowadays. Interestingly, the idea to apply bacteria wittingly or unwittingly dates back to ancient times and was revived in the 19th century mainly by the pioneer William Coley. This review summarizes and compares the results of the past 150 years in bacteria mediated tumor therapy from preclinical to clinical studies. Lessons we have learned from the past provide a solid foundation on which to base future efforts. In this regard, several perspectives are discussed by which bacteria in addition to their intrinsic antitumor effect can be used as vector systems that shuttle therapeutic compounds into the tumor. Strategic solutions like these provide a sound and more apt exploitation of bacteria that may overcome limitations of conventional therapies.

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Chen, Yuhao, Meng Du, Jinsui Yu, Lang Rao, Xiaoyuan Chen, and Zhiyi Chen. "Nanobiohybrids: A Synergistic Integration of Bacteria and Nanomaterials in Cancer Therapy." BIO Integration 1, no. 1 (June 9, 2020): 25–36. http://dx.doi.org/10.15212/bioi-2020-0008.

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Abstract Cancer is a common cause of mortality in the world. For cancer treatment modalities such as chemotherapy, photothermal therapy and immunotherapy, the concentration of therapeutic agents in tumor tissue is the key factor which determines therapeutic efficiency. In view of this, developing targeted drug delivery systems are of great significance in selectively delivering drugs to tumor regions. Various types of nanomaterials have been widely used as drug carriers. However, the low tumor-targeting ability of nanomaterials limits their clinical application. It is difficult for nanomaterials to penetrate the tumor tissue through passive diffusion due to the elevated tumoral interstitial fluid pressure. As a biological carrier, bacteria can specifically colonize and proliferate inside tumors and inhibit tumor growth, making it an ideal candidate as delivery vehicles. In addition, synthetic biology techniques have been applied to enable bacteria to controllably express various functional proteins and achieve targeted delivery of therapeutic agents. Nanobiohybrids constructed by the combination of bacteria and nanomaterials have an abundance of advantages, including tumor targeting ability, genetic modifiability, programmed product synthesis, and multimodal therapy. Nowadays, many different types of bacteria-based nanobiohybrids have been used in multiple targeted tumor therapies. In this review, firstly we summarized the development of nanomaterial-mediated cancer therapy. The mechanism and advantages of the bacteria in tumor therapy are described. Especially, we will focus on introducing different therapeutic strategies of nanobiohybrid systems which combine bacteria with nanomaterials in cancer therapy. It is demonstrated that the bacteria-based nanobiohybrids have the potential to provide a targeted and effective approach for cancer treatment.

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41

Woong Yoo, Su, Seong Young Kwon, Sae-Ryung Kang, and Jung-Joon Min. "Molecular imaging approaches to facilitate bacteria-mediated cancer therapy." Advanced Drug Delivery Reviews 187 (August 2022): 114366. http://dx.doi.org/10.1016/j.addr.2022.114366.

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42

Moghimipour, Eskandar, Samaneh Abedishirehjin, Maryam Abedini Baghbadorani, and Somayeh Handali. "Bacteria and Archaea: A new era of cancer therapy." Journal of Controlled Release 338 (October 2021): 1–7. http://dx.doi.org/10.1016/j.jconrel.2021.08.019.

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Murphy, Carola, Elizabeth Rettedal, Panos Lehouritis, Ciarán Devoy та Mark Tangney. "Intratumoural production of TNFα by bacteria mediates cancer therapy". PLOS ONE 12, № 6 (29 червня 2017): e0180034. http://dx.doi.org/10.1371/journal.pone.0180034.

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Terrisse, Safae, Laurence Zitvogel, and Guido Kroemer. "Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy." microbial Cell 9, no. 12 (December 5, 2022): 202–6. http://dx.doi.org/10.15698/mic2022.12.787.

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Prostate cancer (PC) can be kept in check by androgen deprivation therapy (ADT, usually with the androgen synthesis inhibitor abiraterone acetate or the androgen receptor antagonist such as enzalutamide) until the tumor evolves to castration-resistant prostate cancer (CRPC). The transition of hormone-sensitive PC (HSPC) to CPRC has been explained by cancer cell-intrinsic resistance mechanisms. Recent data indicate that this transition is also marked by cancer cell-extrinsic mechanisms such as the failure of ADT-induced PC immunosurveillance, which depends on the presence of immunostimulatory bacteria in the gut. Moreover, intestinal bacteria that degrade drugs used for ADT, as well as bacteria that produce androgens, can interfere with the efficacy of ADT. Thus, specific bacteria in the gut serve as a source of testosterone, which accelerates prostate cancer progression, and men with CRPC exhibit an increased abundance of such bacteria with androgenic functions. In conclusion, the response of PC to ADT is profoundly influenced by the composition of the microbiota with its immunostimulatory, immunosuppressive and directly ADT-subversive elements.

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45

Pignatelli, Pamela, Federica Maria Romei, Danilo Bondi, Michele Giuliani, Adriano Piattelli, and Maria Cristina Curia. "Microbiota and Oral Cancer as A Complex and Dynamic Microenvironment: A Narrative Review from Etiology to Prognosis." International Journal of Molecular Sciences 23, no. 15 (July 28, 2022): 8323. http://dx.doi.org/10.3390/ijms23158323.

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A complex balanced equilibrium of the bacterial ecosystems exists in the oral cavity that can be altered by tobacco smoking, psychological stressors, bad dietary habit, and chronic periodontitis. Oral dysbiosis can promote the onset and progression of oral squamous cell carcinoma (OSCC) through the release of toxins and bacterial metabolites, stimulating local and systemic inflammation, and altering the host immune response. During the process of carcinogenesis, the composition of the bacterial community changes qualitatively and quantitatively. Bacterial profiles are characterized by targeted sequencing of the 16S rRNA gene in tissue and saliva samples in patients with OSCC. Capnocytophaga gingivalis, Prevotella melaninogenica, Streptococcus mitis, Fusobacterium periodonticum, Prevotella tannerae, and Prevotella intermedia are the significantly increased bacteria in salivary samples. These have a potential diagnostic application to predict oral cancer through noninvasive salivary screenings. Oral lactic acid bacteria, which are commonly used as probiotic therapy against various disorders, are valuable adjuvants to improve the response to OSCC therapy.

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46

Beltran, Julián F., SM Viafara-Garcia, Alberto P. Labrador, and Johan Basterrechea. "The Role of Periodontopathogens and Oral Microbiome in the Progression of Oral Cancer. A Review." Open Dentistry Journal 15, no. 1 (August 24, 2021): 367–76. http://dx.doi.org/10.2174/1874210602115010367.

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Chronic periodontal disease and oral bacteria dysbiosis can lead to the accumulation of genetic mutations that eventually stimulate Oral Squamous Cell Cancer (OSCC). The annual incidence of OSCC is increasing significantly, and almost half of the cases are diagnosed in an advanced stage. Worldwide there are more than 380,000 new cases diagnosed every year, and a topic of extensive research in the last few years is the alteration of oral bacteria, their compositional changes and microbiome. This review aims to establish the relationship between bacterial dysbiosis and OSCC. Several bacteria implicated in periodontal disease, including Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, and some Streptococcus species, promote angiogenesis, cell proliferation, and alteration in the host defense process; these same bacteria have been present in different stages of OSCC. Our review showed that genes involved in bacterial chemotaxis, the lipopolysaccharide (LPS) of the cell wall membrane of gram negatives bacteria, were significantly increased in patients with OSCC. Additionally, some bacterial diversity, particularly with Firmicutes, and Actinobacteria species, has been identified in pre-cancerous stage samples. This review suggests the importance of an early diagnosis and more comprehensive periodontal therapy for patients by the dental care professional.

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47

Ivanenko, N. "BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review." Medical Science of Ukraine (MSU) 17, no. 1 (March 30, 2021): 104–20. http://dx.doi.org/10.32345/2664-4738.1.2021.13.

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Relevance. Treatment of solid tumors and biofilm-derived infections face a common problem: drugs often fail to reach and kill cancer cells and microbial pathogens because of local microenvironment heterogeneities. There are remarkable challenges for current and prospective anticancer and antibiofilm agents to target and maintain activity in the microenvironments where cancer cells and microbial pathogens survive and cause the onset of disease. Bacterial infections in cancer formation will increase in the coming years. Collection of approaches such as ROS modulation in cells, the tumor is promoted by microbe’s inflammation can be a strategy to target cancer and bacteria. Besides that, bacteria may take the advantage of oxygen tension and permissive carbon sources, therefore the tumor microenvironment (TM) becomes a potential refuge for bacteria. It is noteworthy that the relationship between cancer and bacteria is intertwined. Objective: To analyze similarities between biofilm and tumor milieu that is produced against stress conditions and heterogeneous microenvironment for a combination of approaches the bacteriotherapy with chemotherapy which can help in defeating the tumor heterogeneity accompanied with malignancy, drug-resistance, and metastasis. Method: An analytical review of the literature on keywords from the scientometric databases PubMed, Wiley. Results: Bacteria evade antimicrobial treatment is mainly due to persistence that has become dormant during the stationary phase and tolerance. Drug-tolerant persisters and cellular dormancy are crucial in the development of cancer, especially in understanding the development of metastases as a late relapse. Bioﬁlms are formed by groups of cells in diﬀerent states, growing or non-growing and metabolically active or inactive in variable fractions, depending on maturity and on chemical gradients (O2 and nutrients) of the bioﬁlms producing physiological heterogeneity. Heterogeneity in the microenvironment of cancer can be described as a non-cell autonomous driver of cancer cell diversity; in a highly diverse microenvironment, different cellular phenotypes may be selected for or against in different regions of the tumor. Hypoxia, oxidative stress, and inflammation have been identified as positive regulators of metastatic potential, drug resistance, and tumorigenic properties in cancer. It is proven that, Escherichia coli (E. coli) and life-threatening infectious pathogens such as Staphylococcus aureus (SA) and Mycobacterium tuberculosis (Mtb) are noticeably sensitive to alterations in the intracellular oxidative environment. An alternative emerging paradigm is that many cancers may be promoted by commensal microbiota, either by translocation and adherence of microbes to cancer cells or by the distant release of inflammation-activating microbial metabolites. Microbial factors such as F. nucleatum, B. fragilis, and Enterobacteriaceae members may contribute to disease onset in patients with a hereditary form of colorectal cancer (CRC); familial adenomatous polyposis (FAP). These findings are linked with the creation of new biomarkers and therapy for identifying and treating biofilm-associated cancers. Currently, about 20% of neoplasms globally can be caused by infections, with approximately 1.2 million cases annually. Several antineoplastic drugs that exhibited activity against S. mutans, including tamoxifen, doxorubicin, and ponatinib, also possessed activity against other Gram-positive bacteria. Drug repurposing, also known as repositioning, has gained momentum, mostly due to its advantages over de novo drug discovery, including reduced risk to patients due to previously documented clinical trials, lower drug development costs, and faster benchtop-to-clinic transition. Although many bacteria are carcinogens and tumor promoters, some have shown great potential towards cancer therapy. Several species of bacteria have shown an impressive power to penetrate and colonize solid tumors, which has mainly led to neoplasm slower growth and tumor clearance. Different strains of Clostridia, Lactococcus, Bifidobacteria, Shigella, Vibrio, Listeria, Escherichia, and Salmonella have been evaluated against cancer in animal models. Conclusion. Cancer is a multifactorial disease and the use of bacteria for cancer therapy as an immunostimulatory agent or as a vector for carrying the therapeutic cargo is a promising treatment method. Therefore, the world has turned to an alternative solution, which is the use of genetically engineered microorganisms; thus, the use of living bacteria targeting cancerous cells is the unique option to overcome these challenges. Bacterial therapies, whether used alone or combination with chemotherapy, give a positive effect to treat multiple conditions of cancer.

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Al-Hilu, Suad A., and Wisam H. Al-Shujairi. "Dual Role of Bacteria in Carcinoma: Stimulation and Inhibition." International Journal of Microbiology 2020 (August 24, 2020): 1–15. http://dx.doi.org/10.1155/2020/4639761.

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Although what unifies the carcinogenic microorganisms has not been determined by multiple studies, the role of bacteria in the development of neoplasms has not been properly elucidated. In this review, we discuss links between the bacterial species and cancer, with focus on immune responses for the stimulation of tumor cells such as induction of inflammation. Finally, we will describe the potential therapeutic strategies of bacteria on target tumors to improve treatment while mitigating adverse reactions. Cancer is a series of genetic changes that transform normal cells into tumor cells. These changes come from several reasons, including smoking, drinking alcohol, sunlight, exposure to chemical or physical factors, and finally chronic infection with microorganisms, including bacteria. In fact, bacterial infections are not carcinogenic, but recently it was discovered that the association between bacteria and cancer is through two mechanisms, the first stimulating chronic inflammation and the second producing carcinogenic metabolites. While bacteria are carcinogenic agents also, they have a dual role eliminating and removing tumor cells. However, the traditional cancer treatments that include chemotherapy, radiotherapy, surgery, and immunotherapy increase the chances of survival, and there are many side effects of these therapies, including the high toxicity of tissues and normal cells, could not penetrate the tumor cells, and resistance of these therapies by tumor cells. Therefore, the world has turned to an alternative solution, which is the use of genetically engineered microorganisms; thus, the use of living bacteria targeting cancerous cells is the unique option to overcome these challenges. Bacterial therapies, whether used alone or combination with chemotherapy, give a positive effect to treat multiple conditions of cancer. Also, bacteria can be used as vectors for drug, gene, or therapy, and this is a great step to treat cancer. Thus, we review the mechanisms underlying the interaction of the microbiota residents with cancer. Cancer-associated bacteria differ from those in healthy human and are linked with gene-expression profile. We also discuss how live bacteria interact with tumor microenvironments to induce tumor regression through colonization and spread. Finally, we provide past and ongoing clinical trials that include bacteria targeting tumors.

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Becerra-Báez, Elayne Irene, Sergio Enrique Meza-Toledo, Paola Muñoz-López, Luis Fernando Flores-Martínez, Karla Fraga-Pérez, Kevin Jorge Magaño-Bocanegra, Uriel Juárez-Hernández, Armando Alfredo Mateos-Chávez, and Rosendo Luria-Pérez. "Recombinant Attenuated Salmonella enterica as a Delivery System of Heterologous Molecules in Cancer Therapy." Cancers 14, no. 17 (August 30, 2022): 4224. http://dx.doi.org/10.3390/cancers14174224.

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Over a century ago, bacterial extracts were found to be useful in cancer therapy, but this treatment modality was obviated for decades. Currently, in spite of the development and advances in chemotherapies and radiotherapy, failure of these conventional treatments still represents a major issue in the complete eradication of tumor cells and has led to renewed approaches with bacteria-based tumor therapy as an alternative treatment. In this context, live-attenuated bacteria, particularly Salmonella enterica, have demonstrated tumor selectivity, intrinsic oncolytic activity, and the ability to induce innate or specific antitumor immune responses. Moreover, Salmonella enterica also has strong potential as a delivery system of tumor-associated antigens, cytotoxic molecules, immunomodulatory molecules, pro-apoptotic proteins, and nucleic acids into eukaryotic cells, in a process known as bactofection and antitumor nanoparticles. In this review, we present the state of the art of current preclinical and clinical research on the use of Salmonella enterica as a potential therapeutic ally in the war against cancer.

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Umer, Brittany, David Good, Jozef Anné, Wei Duan, and Ming Q. Wei. "Clostridial Spores for Cancer Therapy: Targeting Solid Tumour Microenvironment." Journal of Toxicology 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/862764.

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Solid tumour accounts for 90% of all cancers. The current treatment approach for most solid tumours is surgery, however it is limited to early stage tumours. Other treatment options such as chemotherapy and radiotherapy are non-selective, thus causing damage to both healthy and cancerous tissue. Past research has focused on understanding tumour cells themselves, and conventional wisdom has aimed at targeting these cells directly. Recent research has shifted towards understanding the tumour microenvironment and it’s differences from that of healthy cells/tissues in the body and then to exploit these differences for treatmeat of the tumour. One such approach is utilizing anaerobic bacteria. Several strains of bacteria have been shown to selectively colonize in solid tumours, making them valuable tools for selective tumour targeting and destruction. Amongst them, the anaerobicClostridiumhas shown great potential in penetration and colonization of the hypoxic and necrotic areas of the tumour microenvironment, causing significant oncolysis as well as enabling the delivery of therapeutics directly to the tumourin situ. Various strategies utilizingClostridiumare currently being investigated, and represent a novel area of emerging cancer therapy. This review provides an update review of tumour microenvironment as well as summary of the progresses and current status of Clostridial spore-based cancer therapies.

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