Editorial: Understanding the Impact of Microbes on Tumor Progression and Prevention—Unveiling New Avenues for Cancer Therapy

Vikas Somani^1*Somya Aggarwal¹Rajni Garg²Yoshiko Takeuchi¹Samer Singh³

• ¹School of Medicine, Washington University in St. Louis, St. Louis, United States
• ²Department of Human Genetics and Molecular Medicine, Amity Institute of Health Sciences, Amity University Punjab, Mohali, India, Mohali, India
• ³Banaras Hindu University Institute of Medical Sciences, Varanasi, India

The intricate interplay between the human microbiome and host physiology has emerged as a pivotal area of biomedical research. Microbial communities, regarded as passive colonizers for long, are now recognized as active modulators of diseases, like cancer. This Research Topic, "Understanding the Impact of Microbes on Tumor Progression and Prevention: Unveiling New Avenues for Cancer Therapy," compiles a set of studies that illuminate the diverse roles of microbes in shaping tumor biology. Together, these contributions highlight the dualistic nature of microbes as both facilitators and inhibitors of tumorigenesis and underscore their potential as therapeutic targets, biomarkers, and modulators of treatment responses. The collection begins with a comprehensive review by Lin and Zhang1. This work systematically evaluates bacterial contributions to the metastatic cascade. The authors illustrate how bacteria promote tumor spread by inducing chronic inflammation, modulating the extracellular matrix, and enabling tumor cells to evade immune surveillance. At the same time, probiotics and engineered bacterial strains show the capacity to suppress metastasis, evidencing the bidirectional nature of microbial influence on cancer progression. This duality exemplifies the broader theme of the Research Topic, i.e., microbes as both potential drivers and therapeutic allies in oncology. Focusing on ovarian cancer, Zhang et al. explore how microbial alterations modulate local inflammation within the tumor microenvironment2. Their analysis highlights the importance of microbial dysbiosis in sustaining pro-inflammatory signals that support tumor growth. By linking microbial shifts with immune modulation, the article emphasizes a translational opportunity: leveraging microbiome-targeted interventions for both therapeutic development and early screening. This mechanistic perspective positions microbial– immune interactions as a focal point for future ovarian cancer strategies. The relationship between microbes and cancer therapy is further illustrated by Chrisman et al., in "Ionizing radiation improves skin bacterial dysbiosis in cutaneous T-cell lymphoma"3 Their longitudinal study demonstrates that total skin electron beam therapy (TSEBT), a standard treatment for CTCL, exerts effects beyond cytoreduction. Radiotherapy restored microbial community balance, reducing dominance of Staphylococcus aureus and facilitating recolonization by beneficial commensals. These findings propose an additional therapeutic dimension: radiation may partly act by correcting microbial dysbiosis and improving skin barrier function. By situating microbiome restoration within the context of cancer treatment, this study broadens our understanding of radiation's multifaceted mechanism of action3. In line with the theme of microbial modulation of therapy, De Re et al. in their study demonstrated that virulent H. pylori strains can disrupt host DNA repair pathways while promoting immune evasion via PD-L2 upregulation. Such microbial interference could undermine the efficacy of HER2-targeted treatments, complicating therapeutic predictability. Importantly, the findings raise the possibility that unaddressed microbial infections may influence targeted therapy outcomes, emphasizing the need to integrate microbial status into clinical decision-making for gastric cancer4. Further insight into microbe-driven cancer progression is provided by Li et al., who investigate the role of Fusobacterium nucleatum in colorectal cancer5. Their study identifies Serpine2 as a key factor upregulated by bacterial influence, promoting fibroblast–epithelial communication and tumor progression. These observations highlight microbial shaping of stromal dynamics, suggesting that disrupting such microbe-induced crosstalk could provide a novel therapeutic strategy in colorectal cancer5. Broadening the perspective beyond individual cancer types, Liu et al. offer a pan-cancer analysis in their study6. Through evaluation of 783 tumor samples across seven cancer types, this study reveals widespread intratumoral microbial presence, with recurring genera such as Pseudomonas, Streptococcus, and Prevotella. Moreover, microbial diversity analyses demonstrated significant differences between cancerous and adjacent healthy tissue, particularly in gastric and liver cancers. These findings identify intratumoral microbial signatures as potential pan-cancer biomarkers with diagnostic and prognostic value, suggesting new paths towards microbial signature-based stratification in cancer management6. Viewed collectively, these contributions present a coherent framework positioning the microbiome as a critical determinant of tumor biology. At mechanistic level, microbes may influence tumorigenesis by modulating inflammation, evading immune responses, reprogramming stromal cells, and interfering with cell signalling and repair pathways. On a translational level, microbial signatures are emerging as potential biomarkers for diagnosis, prognosis, and therapeutic response. Importantly, microbial modulation—via radiation, probiotics, engineered strains, or targeted therapies—offers novel possibilities for augmenting standard cancer treatments. Several themes have emerged from this research collection. First, microbial influences are context-dependent, exerting either pro-or anti-tumorigenic effects depending on host state, cancer type, and microbial composition. This underscores the necessity of finely tuned therapeutic strategies that proactively consider microbial ecology. Second, cancer therapies themselves—whether radiation or immune-targeted agents—may shift microbial communities, creating feedback loops that influence clinical outcomes. Finally, at the systems level, conserved microbial signatures across multiple tumor types suggest the possibility of universal microbial biomarkers or targets, opening up the opportunities for broad-spectrum approaches in precision oncology. The implications of these findings are profound. There is a growing recognition that cancer is not solely a disease of malignant cells but a product of ecological networks that include microbial partners. Therapeutic modalities that acknowledge this wider ecosystem— through microbiome correction, exploitation, or monitoring—could transform cancer care. Importantly, future research must integrate longitudinal, mechanistic, and patient-centered approaches to clarify causal relationships and define actionable strategies. In summary, this collection of seven studies illustrates the breadth and depth of microbial involvement in cancer (Table-1). From ovarian to colorectal and cutaneous malignancies, from localized therapeutic effects to pan-cancer microbial patterns, the evidence consistently highlights microbes as integral elements of the tumor microenvironment. By unraveling these complex host–microbe interactions, we move toward a paradigm in which the microbiome is no longer peripheral but central to cancer biology and therapy. As the field advances, microbial signatures and interventions may form the foundation of next-generation diagnostic and therapeutic platforms, ultimately bringing us closer to personalized and effective strategies for cancer prevention and treatment. Table-1: Overview of Contributions in the Special Issue Therapeutic Target/Strategy Mechanism/Rationale Cancer Type(s) Contributing Article Microbiome-Targeted Therapies Modulating the tumor's inflammatory microenvironment by altering microbial composition. Ovarian Cancer Zhang et al2. Therapeutic Target/Strategy Mechanism/Rationale Cancer Type(s) Contributing Article Gut & Intratumoral Microbiota as Biomarkers Using microbial signatures to predict response to triple therapy (lenvatinib + PD-1 inhibitors + local therapy). Hepatocellular Carcinoma (HCC) Lin et al7. Restoration of Skin Microbiome Using therapies like ionizing radiation to reverse dysbiosis, reduce pathogenic bacteria (S. aureus), and increase beneficial commensals. Cutaneous T-cell Lymphoma (CTCL) Chrisman et al3. PD-L2 and DNA Repair Pathways Targeting immune evasion pathways (PD-L2) and DNA repair machinery (MSH6) that are modulated by H. pylori infection. HER2-Positive Gastric Cancer De Re et al4. Serpine2 Molecule Inhibiting Serpine2, a key molecule upregulated by F. nucleatum that enhances fibroblast-epithelial cell communication to promote tumor progression. Colon Cancer Li et al5. Probiotics & Engineered Bacteria Utilizing beneficial microbes to inhibit metastasis by modulating the immune response and remodeling the tumor microenvironment. General (Review) Lin and Zhang1 Pan-Cancer Microbial Diversity as Biomarkers Using intratumoral microbial diversity indices (Shannon, Simpson) and common bacterial genera (Pseudomonas, Streptococcus, Prevotella) for diagnosis and prognosis across multiple cancer types. Multiple Cancers (Breast, Esophageal, Gastric, Liver, Lung, Pancreatic, OSCC) Liu et al6.