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Bacteria, stem cells and cancer

Cancer Gene Therapy volume 32, pages 269–272 (2025)Cite this article

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Roughly 15% of all cancers are attributable to infections, a percentage that soars in developing countries [1]. Among the pathogens recognized as having an etiologic role in cancer, viruses (especially HPV, HBV, and HCV) play the largest share, but one single bacteria, Helicobacter Pylori, accounts for almost 40% of cases worldwide. While raising hopes for prevention opportunities, these numbers expose our still limited understanding of carcinogenesis by biological agents.

Viral carcinogenesis has guided the development of molecular biology and led to historical breakthroughs in identifying oncogenes and their downstream signaling cascades, as well as molecular tumor suppressive circuitries subverted in malignancy [2]. Bacterial carcinogenesis, epitomized by the role of H. Pylori (HP) in gastric malignancy (Adenocarcinoma and MALT lymphoma), has highlighted the importance of chronic inflammation in the initiation and promotion of tumorigenesis; however, with some exceptions [3], cellular mechanisms and molecular underpinnings of bacteria-driven tumorigenesis have long remained elusive. Lately, prompted by two decades of impressive advances in the characterization and classification of resident microbial communities throughout the body and even within cancer tissues, bacterial carcinogenesis has emerged as one of the hottest topics in biomedical research. These efforts have not only unraveled the potential role of luminal (i.e., fecal) and cell-bound bacteria in GI-associated (i.e., Colorectal, Pancreatic, and Gallbladder) cancers, but also involved microbes in neoplasms of supposedly sterile (i.e., brain, bone, ovary) tissues [4,5,6]. Although H. Pylori remains nowadays the only bacterial pathogen recognized as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer (IARC), species like F. nucleatum (Fn), Bacteroides Fragilis (BF) and pks + E. Coli (EC) surfaced as prominent suspects for the initiation ad/or promotion of gastrointestinal and other cancers [7]. Major mechanisms of bacteria-driven tumorigenesis, often shared across different pathogens and tumors, include (a) DNA damage (genotoxicity); (b) receptor-mediated activation of oncogenic signaling pathways sustaining cancer cell growth/survival, motility and resistance to therapy; (c) cell metabolic and epigenetic rewiring by bacteria-released metabolites; (d) influence on tumor microenvironment (TME) and interference with antitumor immunity (see excellent recent reviews like [3] and [8] for specific references).

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Fig. 1: Bacteria activate epithelial stem cells in wound repair and cancer.

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Acknowledgements

Original research performed in the author’s laboratory was funded by the Italian Ministry of University and Research, PRIN – Bando 2022 PNRR Prot. P202243FBL, and Università Cattolica del Sacro Cuore intramural grant D3.2 2021.

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  1. Department of Translational Medicine and Surgery, Faculty of Medicine, Università Cattolica del Sacro Cuore, Rome, Italy

    Giovambattista Pani

  2. Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Giovambattista Pani

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Correspondence to Giovambattista Pani.

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Pani, G. Bacteria, stem cells and cancer. Cancer Gene Ther 32, 269–272 (2025). https://doi.org/10.1038/s41417-025-00876-x

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