{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T22:46:21Z","timestamp":1788907581572,"version":"build-2803163510"},"reference-count":91,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Cancer remains one of the leading causes of morbidity and mortality worldwide, and despite major advances in surgery, chemotherapy, radiotherapy, and immunotherapy, important therapeutic limitations persist, including systemic toxicity, therapeutic resistance, and poor drug penetration into hypoxic tumor regions. These challenges have renewed interest in alternative biological strategies, particularly the use of bacteria and bacterial toxins as antitumor agents. Certain bacterial species possess intrinsic tumor-targeting properties, including the ability to selectively colonize hypoxic and necrotic regions of solid tumors that are poorly accessible to conventional therapies. This review provides a comprehensive analysis of the mechanisms underlying bacteria-mediated anticancer activity, including selective tumor colonization, direct oncolysis, immune activation, and toxin-mediated cytotoxicity. Both obligate anaerobes (e.g., Clostridium and Bifidobacterium) and facultative anaerobes (e.g., Salmonella, Escherichia coli, and Listeria monocytogenes) are examined for their tumor-targeting potential. In addition, we discuss the oncological applications of several bacterial toxins and toxin-derived therapeutic constructs, including Cytolysin A (ClyA), Clostridium difficile toxin B (TcdB), diphtheria toxin, Pseudomonas aeruginosa exotoxin A, and Clostridium perfringens enterotoxin (CPE). Emerging strategies such as recombinant immunotoxins and bacterial-directed enzyme prodrug therapy (BDEPT) are also reviewed. Finally, current translational challenges, including pharmacokinetic limitations, immune clearance, and biosafety considerations, are analyzed, highlighting future directions for integrating bacteria-based platforms into next-generation cancer therapies. This approach reflects the growing interest in microbial strategies for oncology and underscores the potential of bacteria and their toxins as innovative tools in the development of targeted anticancer therapies.<\/jats:p>","DOI":"10.3390\/microorganisms14050964","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T17:26:18Z","timestamp":1777051578000},"page":"964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Use of Bacteria and Their Toxins as Antitumor Agents: Present and Future"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-5630","authenticated-orcid":false,"given":"Luz","family":"Ibarra-Vel\u00e1zquez","sequence":"first","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas y de la Vida, Centro Universitario de la Ci\u00e9nega, Universidad de Guadalajara, Av. Universidad 1115, Lindavista, Ocotl\u00e1n 47820, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1120-0185","authenticated-orcid":false,"given":"Marco","family":"Cardona-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas y de la Vida, Centro Universitario de la Ci\u00e9nega, Universidad de Guadalajara, Av. Universidad 1115, Lindavista, Ocotl\u00e1n 47820, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0381-7995","authenticated-orcid":false,"given":"Reynaldo","family":"Cervantes-Figueroa","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas y de la Vida, Centro Universitario de la Ci\u00e9nega, Universidad de Guadalajara, Av. Universidad 1115, Lindavista, Ocotl\u00e1n 47820, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Ascencio-Navarrate","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas y de la Vida, Centro Universitario de la Ci\u00e9nega, Universidad de Guadalajara, Av. Universidad 1115, Lindavista, Ocotl\u00e1n 47820, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5303-8623","authenticated-orcid":false,"given":"Mar\u00eda","family":"Becerra-Mercado","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas y de la Vida, Centro Universitario de la Ci\u00e9nega, Universidad de Guadalajara, Av. Universidad 1115, Lindavista, Ocotl\u00e1n 47820, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5260-9139","authenticated-orcid":false,"given":"Ana","family":"Madriz-Elisondo","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias M\u00e9dicas y de la Vida, Centro Universitario de la Ci\u00e9nega, Universidad de Guadalajara, Av. Universidad 1115, Lindavista, Ocotl\u00e1n 47820, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sawant, S.S., Patil, S.M., Gupta, V., and Kunda, N.K. (2020). Microbes as Medicines: Harnessing the Power of Bacteria in Advancing Cancer Treatment. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207575"},{"key":"ref_4","first-page":"7","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_5","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth","volume":"41","author":"Joyce","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41551-025-01459-9","article-title":"Tumour-resident oncolytic bacteria trigger potent anticancer effects through selective intratumoural thrombosis and necrosis","volume":"10","author":"Iwata","year":"2025","journal-title":"Nat. Biomed. Eng."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/nrc1456","article-title":"High interstitial fluid pressure\u2014An obstacle in cancer therapy","volume":"4","author":"Heldin","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0297-0","article-title":"Bacteria-cancer interactions: Bacteria-based cancer therapy","volume":"51","author":"Duong","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gupta, K.H., Nowicki, C., Giurini, E.F., Marzo, A.L., and Zloza, A. (2021). Bacterial-based cancer therapy (BBCT): Recent advances, current challenges, and future prospects for cancer immunotherapy. Vaccines, 9.","DOI":"10.3390\/vaccines9121497"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Singh, S., Kim, G.H., Baek, K.R., and Seo, S.O. (2025). Anti-Cancer Strategies Using Anaerobic Spore-Forming Bacteria Clostridium: Advances and Synergistic Approaches. Life, 15.","DOI":"10.3390\/life15030465"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wei, X., Du, M., Chen, Z., and Yuan, Z. (2022). Recent Advances in Bacteria-Based Cancer Treatment. Cancers, 14.","DOI":"10.3390\/cancers14194945"},{"key":"ref_13","first-page":"154","article-title":"The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas","volume":"26","author":"McCarthy","year":"2006","journal-title":"Iowa Orthop. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"110393","DOI":"10.1016\/j.biopha.2020.110393","article-title":"Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect","volume":"129","author":"Han","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e00194-23","DOI":"10.1128\/cmr.00194-23","article-title":"Review of BCG immunotherapy for bladder cancer","volume":"38","author":"Liatsos","year":"2025","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jare.2023.09.003","article-title":"AI-2 quorum sensing controlled delivery of cytolysin-A by tryptophan auxotrophic low-endotoxic Salmonella and its anticancer effects in CT26 mice with colon cancer","volume":"61","author":"Aganja","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_17","first-page":"1957","article-title":"Tumor Response to Ionizing Radiation Combined with Antiangiogenesis or Vascular Targeting Agents: Exploring Mechanisms of Interaction1","volume":"9","author":"Wachsberger","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, T., Yu, X.-M., Yang, S.-T., and Zhou, W.-W. (2025). Gut Bacteria-Based Cancer Therapy and Anti-Solid Tumor Mechanisms. Microbiol. Res., 16.","DOI":"10.3390\/microbiolres16050092"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Dailey, K.M., Jacobson, R.I., Johnson, P.R., Woolery, T.J., Kim, J., Jansen, R.J., Mallik, S., and Brooks, A.E. (2021). Methods and Techniques to Facilitate the Development of Clostridium novyi NT as an Effective, Therapeutic Oncolytic Bacteria. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.624618"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.semcancer.2024.03.003","article-title":"Hypoxia-targeting bacteria in cancer therapy","volume":"100","author":"Staedtke","year":"2024","journal-title":"Semin. Cancer Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Leschner, S., Westphal, K., Dietrich, N., Viegas, N., Jablonska, J., Lyszkiewicz, M., Lienenklaus, S., Falk, W., Gekara, N., and Loessner, H. (2009). Tumor invasion of Salmonella enterica serovar Typhimurium is accompanied by strong hemorrhage promoted by TNF-\u03b1. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006692"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20251076","DOI":"10.1515\/biol-2025-1076","article-title":"Oncolytic bacteria: A revolutionary approach to cancer therapy","volume":"20","author":"Khormi","year":"2025","journal-title":"Open Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s40164-023-00442-x","article-title":"Role of gut microbiome in cancer immunotherapy: From predictive biomarker to therapeutic target","volume":"12","author":"Zhang","year":"2023","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1177\/153303460500400402","article-title":"Cancer Gene Therapy","volume":"4","author":"Yamamoto","year":"2005","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11680","DOI":"10.1038\/s41598-019-48285-z","article-title":"A novel Carcinoembryonic Antigen (CEA)-Targeted Trimeric Immunotoxin shows significantly enhanced Antitumor Activity in Human Colorectal Cancer Xenografts","volume":"9","author":"Navarro","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00063030-200923010-00001","article-title":"Recombinant Immunotoxins Containing Truncated Bacterial Toxins for the Treatment of Hematologic Malignancies","volume":"23","author":"Kreitman","year":"2009","journal-title":"BioDrugs"},{"key":"ref_27","first-page":"739","article-title":"The systemic administration of lethal toxin achieves a growth delay of human melanoma and neuroblastoma xenografts: Assessment of receptor contribution","volume":"32","author":"Rouleau","year":"2008","journal-title":"Int. J. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1042\/BJ20061891","article-title":"Manipulation of host signalling pathways by anthrax toxins","volume":"402","author":"Turk","year":"2007","journal-title":"Biochem. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.tim.2005.01.002","article-title":"Cyclomodulins: Bacterial effectors that modulate the eukaryotic cell cycle","volume":"13","author":"Taieb","year":"2005","journal-title":"Trends Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.biopha.2018.02.045","article-title":"Clostridium difficile toxin B recombinant protein inhibits tumor growth and induces apoptosis through inhibiting Bcl-2 expression, triggering inflammatory responses and activating C-erbB-2 and Cox-2 expression in breast cancer mouse model","volume":"101","author":"Zhang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Huang, T., Li, S., Li, G., Tian, Y., Wang, H., Shi, L., Perez-Cordon, G., Mao, L., Wang, X., and Wang, J. (2014). Utility of Clostridium difficile toxin B for inducing anti-tumor immunity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110826"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1128\/IAI.01705-06","article-title":"Difference in the cytotoxic effects of toxin B from Clostridium difficile strain VPI 10463 and toxin B from variant Clostridium difficile strain 1470","volume":"75","author":"Huelsenbeck","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.mam.2006.12.001","article-title":"Suicide genes for cancer therapy","volume":"28","author":"Portsmouth","year":"2007","journal-title":"Mol. Asp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.1016\/j.vaccine.2009.04.041","article-title":"The first clinical use of a live-attenuated Listeria monocytogenes vaccine: A Phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix","volume":"27","author":"Maciag","year":"2009","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15083","DOI":"10.1073\/pnas.2036598100","article-title":"Overcoming the hypoxic barrier to radiation therapy with anaerobic bacteria","volume":"100","author":"Bettegowda","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1002\/cncr.28875","article-title":"Phase 1 study of the antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front-line therapy of pleural mesothelioma and correlation of tumor response with serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125","volume":"120","author":"Hassan","year":"2014","journal-title":"Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1056\/NEJMoa1815105","article-title":"Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm","volume":"380","author":"Pemmaraju","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1158\/1078-0432.CCR-20-2065","article-title":"Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors","volume":"27","author":"Janku","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1200\/JCO.2002.20.1.142","article-title":"Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma","volume":"20","author":"Toso","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1097\/IGC.0000000000001235","article-title":"A Randomized Phase 2 Study of ADXS11-001 Listeria monocytogenes-Listeriolysin O Immunotherapy with or Without Cisplatin in Treatment of Advanced Cervical Cancer","volume":"28","author":"Basu","year":"2018","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40661-017-0046-9","article-title":"Mechanistic insights into ADXS11-001 human papillomavirus-associated cancer immunotherapy","volume":"4","author":"Miles","year":"2017","journal-title":"Gynecol. Oncol. Res. Pract."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Murase, K. (2022). Cytolysin A (ClyA): A bacterial virulence factor with potential applications in nanopore technology, vaccine development, and tumor therapy. Toxins, 14.","DOI":"10.3390\/toxins14020078"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.ymthe.2021.08.023","article-title":"Targeting of pancreatic cancer cells and stromal cells using engineered oncolytic Salmonella typhimurium","volume":"30","author":"Tan","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7437","DOI":"10.1158\/1078-0432.CCR-06-2019","article-title":"Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human melanoma tumors in athymic nude mice","volume":"12","author":"Singh","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.taap.2014.06.010","article-title":"Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities","volume":"279","author":"Peters","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1002\/ijc.29632","article-title":"Clostridium perfringens enterotoxin C-terminal domain labeled to fluorescent dyes for in vivo visualization of micrometastatic chemotherapy-resistant ovarian cancer","volume":"137","author":"Cocco","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"981626","DOI":"10.1155\/2012\/981626","article-title":"Use of Clostridium perfringens enterotoxin and the enterotoxin receptor-binding domain (C-CPE) for cancer treatment: Opportunities and challenges","volume":"2012","author":"Gao","year":"2012","journal-title":"J. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.3390\/toxins7041116","article-title":"Clostridium perfringens enterotoxin (CPE) and CPE-binding domain (c-CPE) for the detection and treatment of gynecologic cancers","volume":"7","author":"Black","year":"2015","journal-title":"Toxins"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1349-7006.2006.00221.x","article-title":"Genetically engineered Bifidobacterium longum for tumor-targeting enzyme-prodrug therapy of autochthonous mammary tumors in rats","volume":"97","author":"Sasaki","year":"2006","journal-title":"Cancer Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1271\/bbb.70284","article-title":"Exogeneous cytosine deaminase gene expression in Bifidobacterium breve I-53-8w for tumor-targeting enzyme\/prodrug therapy","volume":"71","author":"Hidaka","year":"2007","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/sj.cgt.7700303","article-title":"Specific targeting of cytosine deaminase to solid tumors by engineered Clostridium acetobutylicum","volume":"8","author":"Theys","year":"2001","journal-title":"Cancer Gene Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1089\/104303402320139005","article-title":"Tumor-targeted Salmonella expressing cytosine deaminase as an anticancer agent","volume":"13","author":"King","year":"2002","journal-title":"Hum. Gene Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"101620","DOI":"10.1016\/j.mtbio.2025.101620","article-title":"Ultrasound-responsive engineered bacteria mediated specific controlled expression of catalase and efficient radiotherapy","volume":"31","author":"Liu","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Liu, Z., Lim, S.H., Min, J.J., and Jung, S. (2023). Synergistic Antitumor Effect of Combined Radiotherapy and Engineered Salmonella typhimurium in an Intracranial Sarcoma Mouse Model. Vaccines, 11.","DOI":"10.3390\/vaccines11071275"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bon\u00f9, M.L., Georgopulos, A., Ramera, M., Andreuccetti, J., Guerini, A.E., Bozzola, A.M., Morelli, V., Balduzzi, J., Katica, M., and Cefaratti, M. (2025). Microbiota Modulation of Radiosensitiveness and Toxicity in Gastrointestinal Cancers: What Radiation Oncologists Need to Know\u2014A Review on Behalf of the Italian Association of Radiobiology (AIRB). Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47040265"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1186\/s12951-024-02793-x","article-title":"The application of bacteria-nanomaterial hybrids in antitumor therapy","volume":"22","author":"Xiao","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yan, S., Gan, Y., Xu, H., and Piao, H. (2024). Bacterial carrier-mediated drug delivery systems: A promising strategy in cancer therapy. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1526612"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.7150\/thno.35486","article-title":"Opportunities and Challenges for Antibodies against Intracellular Antigens","volume":"9","author":"Yang","year":"2019","journal-title":"Theranostics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1126\/science.add9667","article-title":"Engineering bacteria as interactive cancer therapies","volume":"378","author":"Gurbatri","year":"2022","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.biopha.2017.01.120","article-title":"The role of IL17B-IL17RB signaling pathway in breast cancer","volume":"88","author":"Alinejad","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1128\/CMR.18.2.247-263.2005","article-title":"Clostridium difficile toxins: Mechanism of action and role in disease","volume":"18","author":"Voth","year":"2005","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1128\/IAI.00186-12","article-title":"MAPK-activated protein kinase 2 contributes to Clostridium difficile-associated inflammation","volume":"81","author":"Bobo","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nrmicro2279","article-title":"Shiga toxins\u2014From cell biology to biomedical applications","volume":"8","author":"Johannes","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Liu, Y., Tian, S., Thaker, H., and Dong, M. (2021). Shiga toxins: An update on host factors and biomedical applications. Toxins, 13.","DOI":"10.3390\/toxins13030222"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15406","DOI":"10.1021\/acsomega.3c00667","article-title":"Clickable Shiga toxin B subunit for drug delivery in cancer therapy","volume":"8","author":"Danielewicz","year":"2023","journal-title":"ACS Omega"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Distler, U., Souady, J., Hulsewig, M., Drmic-Hofman, I., Haier, J., Friedrich, A.W., Karch, H., Senninger, N., Dreisewerd, K., and Berkenkamp, S. (2009). Shiga toxin receptor Gb3Cer\/CD77: Tumor-association and promising therapeutic target in pancreas and colon cancer. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006813"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111639","DOI":"10.1016\/j.cbi.2025.111639","article-title":"Shiga toxins from enterohemorrhagic Escherichia coli and anti-GB3 antibody as novel agents against triple negative breast cancer","volume":"419","author":"Pinto","year":"2025","journal-title":"Chem.-Biol. Interact."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Rivas, M., Pichel, M., Zylberman, V., Colonna, M., Valerio, M., Massa, C., Pardo, R., Ciocchini, A.E., Sanguineti, S., and Roubicek, I. (2025). INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome. Toxins, 17.","DOI":"10.3390\/toxins17060282"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nrc1891","article-title":"Immunotoxin therapy of cancer","volume":"6","author":"Pastan","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"106282","DOI":"10.1016\/j.phrs.2022.106282","article-title":"Bacteria-based nanodrug for anticancer therapy","volume":"182","author":"Xie","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1080\/10428190701799035","article-title":"Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia","volume":"49","author":"Frankel","year":"2008","journal-title":"Leuk. Lymphoma"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nrd.2016.268","article-title":"Strategies and challenges for the next generation of antibody\u2013drug conjugates","volume":"16","author":"Beck","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/S1470-2045(21)00139-X","article-title":"Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): A multicentre, open-label, single-arm, phase 2 trial","volume":"22","author":"Caimi","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1016\/S2352-3026(24)00345-4","article-title":"Loncastuximab tesirine with rituximab in patients with relapsed or refractory follicular lymphoma: A single-centre, single-arm, phase 2 trial","volume":"12","author":"Alderuccio","year":"2025","journal-title":"Lancet Haematol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1038\/s41375-018-0210-1","article-title":"Moxetumomab pasudotox in relapsed\/refractory hairy cell leukemia","volume":"32","author":"Kreitman","year":"2018","journal-title":"Leukemia"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s40261-021-01069-8","article-title":"Moxetumomab pasudotox in hairy cell leukaemia: A profile of its use","volume":"41","author":"Kang","year":"2021","journal-title":"Clin. Drug Investig."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3324\/haematol.2018.188888","article-title":"Gemtuzumab ozogamicin for de novo acute myeloid leukemia: Final efficacy and safety updates from the open-label, phase III ALFA-0701 trial","volume":"104","author":"Lambert","year":"2018","journal-title":"Haematologica"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e495","DOI":"10.1016\/S2352-3026(23)00089-3","article-title":"Intensive chemotherapy with or without gemtuzumab ozogamicin in patients with NPM1-mutated acute myeloid leukaemia (AMLSG 09\u201309): A randomised, open-label, multicentre, phase 3 trial","volume":"10","author":"Weber","year":"2023","journal-title":"Lancet Haematol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1182\/blood.2023020630","article-title":"Fractionated vs. single-dose gemtuzumab ozogamicin with determinants of benefit in older patients with AML: The UK NCRI AML18 trial","volume":"142","author":"Freeman","year":"2023","journal-title":"Blood"},{"key":"ref_80","first-page":"5188","article-title":"Sparse initial entrapment of systemically injected Salmonella typhimurium leads to heterogeneous accumulation within tumors","volume":"63","author":"Forbes","year":"2003","journal-title":"Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41568-018-0070-z","article-title":"Tumour-targeting bacteria engineered to fight cancer","volume":"18","author":"Zhou","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/imr.12390","article-title":"Immunogenicity of therapeutic recombinant immunotoxins","volume":"270","author":"Mazor","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1104819","article-title":"Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy","volume":"307","author":"Jain","year":"2005","journal-title":"Science"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.ccr.2012.01.007","article-title":"Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma","volume":"21","author":"Provenzano","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/nrc2934","article-title":"Engineering the perfect (bacterial) cancer therapy","volume":"10","author":"Forbes","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"8451728","DOI":"10.1155\/2016\/8451728","article-title":"Bacteria in Cancer Therapy: Renaissance of an Old Concept","volume":"2016","author":"Felgner","year":"2016","journal-title":"Int. J. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nrmicro.2017.172","article-title":"Engineering bacteria for diagnostic and therapeutic applications","volume":"16","author":"Riglar","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.7150\/thno.125301","article-title":"Advances in the engineering of living probiotics for cancer immunotherapy","volume":"16","author":"Muhammad","year":"2026","journal-title":"Theranostics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/s41589-022-00993-w","article-title":"Enzymatic assembly of the salinosporamide \u03b3-lactam-\u03b2-lactone anticancer warhead","volume":"18","author":"Bauman","year":"2022","journal-title":"Nat. Chem. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1126\/science.adf3974","article-title":"Engineered bacteria detect tumor DNA","volume":"381","author":"Cooper","year":"2023","journal-title":"Science"},{"key":"ref_91","first-page":"e151574","article-title":"Design and Characterization of Ricin Based Immunotoxins Against EPHA2 Receptor for Breast Cancer Therapy: An In-Silico Study","volume":"24","author":"Faraz","year":"2025","journal-title":"Iran. J. Pharm. Res. IJPR"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/5\/964\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T15:18:29Z","timestamp":1777475909000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/5\/964"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":91,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["microorganisms14050964"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14050964","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]}}}