Aug 2026· Asian Journal of Research in Biochemistry· 0 citations
TL;DR
This critical narrative review evaluates tumour-targeting bacteria, engineered bacterial therapeutics, oncolytic viruses and manipulation of the host microbiome from a molecular-biology perspective.
Abstract
Microbial interventions are being developed as anticancer agents, local drug factories, replicating immunotherapies and modifiers of treatment response. Their appeal arises from properties that conventional medicines do not readily reproduce: active replication, environmental sensing, penetration of poorly perfused tissue, programmable payload production and the capacity to engage innate and adaptive immunity. This critical narrative review evaluates tumour-targeting bacteria, engineered bacterial therapeutics, oncolytic viruses and manipulation of the host microbiome from a molecular-biology perspective. Literature published from 1 January 1990 to 29 May 2026 was selected through a transparent search of PubMed/MEDLINE, reference chaining and bibliographic verification of article identity and Digital Object Identifiers. The evidence indicates that microbial therapies operate through partially shared molecular modules: selective localisation or replication, pattern-recognition receptor signalling, immunogenic cell injury, antigen release and cross-presentation, metabolic reprogramming, and spatially restricted expression of therapeutic cargo. Yet the maturity of evidence differs sharply across platforms. Bacillus Calmette–Guérin and talimogene laherparepvec demonstrate that live microbial products can achieve clinical utility, whereas most engineered bacteria remain supported mainly by murine models and early-phase studies. Oncolytic viruses have produced durable responses in selected settings, but apparently strong phase I or II signals have not always translated into improved survival in randomised trials. Gut-microbiome associations with immune-checkpoint inhibitor outcomes are reproducible at a broad ecological level but inconsistent at the level of individual taxa; early faecal microbiota transplantation studies provide proof of principle rather than definitive efficacy. Across platforms, the central translational problem is not simply potency but control: biodistribution, genetic stability, inflammatory dose, immune clearance, manufacturing consistency and reversibility must be treated as molecular design variables. Progress will depend on mechanism-linked biomarkers, standardised pharmacodynamic measurements, rational combination trials and containment architectures that are validated under clinically realistic conditions.
A conceptual framework for harnessing living therapeutics to convert immunologically “cold” tumors into “hot”, therapy-sensitive lesions is provided and an AI-guided, microbiome-integrated framework to accelerate clinical translation is proposed.
Jin-Hui Guo, Yi-Meng Li, Yueqi Yang et al.· Frontiers in Immunology· 0 citations
Current evidence supports bacteria as a promising precision modality, particularly for immunologically “cold” or hypoxic tumors; however, major challenges remain in the predictability of intratumoral distribution, host clearance, genetic stability, and long-term safety.
Arman H. Sharifi, Ngoc Hai Trieu Phong, Anjali Marek et al.· Molecular Biomedicine· 0 citations
This review systematically explores the dual roles of tumor‐associated microbiota‐both promoting and suppressing malignancy‐and highlights the transformative potential of engineered bacterial systems in cancer treatment, and discusses innovative strategies in which bacteria are harnessed to remodel the immunosuppressive tumor microenvironment, potentiate immune checkpoint therapies, and synergize with conventional modalities.
This review highlights chassis selection, circuit architectures, applications for metabolic diseases and cancer, metabolic bottlenecks, and future directions for precision microbial therapeutics for metabolic disorders and oncology.
B. Onoja, S. Agada, Waheeb S. Aggad et al.· Microbiology Research· 0 citations
Background The human microbiome is an abundant reservoir of bioactive molecules with considerable therapeutic potential in oncology. Among these microbial products, bacteriocins and other postbiotic metabolites have emerged as promising anticancer agents due to their diverse biological activities and ability to modulate multiple cancer-related pathways. Growing evidence suggests that microbiome-derived compounds may provide novel opportunities for the development of safer and more targeted cancer therapeutics. Objectives This review aims to comprehensively evaluate the current knowledge on bacteriocins and postbiotic metabolites as anticancer agents, highlighting their sources, structural and functional properties, mechanisms of action, computational-assisted discovery approaches, nanotechnology-based delivery systems, and challenges associated with clinical translation. Methods A critical analysis of the available literature was conducted to summarize the biological characteristics of bacteriocin-producing microorganisms, the classification and mechanisms of bacteriocins, and the anticancer activities of major postbiotic metabolites. Recent advances in molecular docking, molecular dynamics simulations, systems biology, artificial intelligence, and nanotechnology-based drug delivery platforms were also examined to assess their contributions to therapeutic development. Results Bacteriocins exhibit anticancer effects through multiple mechanisms, including disruption of cancer cell membranes, induction of apoptosis, regulation of oxidative stress, inhibition of cell proliferation, suppression of angiogenesis and metastasis, epigenetic modulation, and enhancement of antitumor immune responses. In addition, postbiotic metabolites such as short-chain fatty acids, indole derivatives, reuterin, and microbial exopolysaccharides contribute to tumour suppression and modulation of host–microbe interactions. Computational approaches have accelerated the identification and optimization of bacteriocin-derived therapeutic candidates, while nanotechnology-based delivery systems have improved their stability, bioavailability, and tumour-targeting capabilities. Nevertheless, challenges including limited clinical evidence, non-standardized experimental methodologies, poor pharmacokinetic properties, manufacturing constraints, and regulatory barriers remain significant obstacles to clinical implementation. Conclusion Bacteriocins and postbiotic metabolites represent a versatile and promising class of microbiome-derived anticancer agents with substantial potential for precision oncology. The integration of microbiome science, synthetic biology, computational drug discovery, and advanced drug delivery technologies is expected to facilitate the translation of these natural compounds into clinically effective cancer therapeutics. Future research should focus on mechanistic validation, large-scale production, pharmacological optimization, and well-designed clinical studies to accelerate their development and therapeutic application.
Radhamanalan Guhanraj· Frontiers in Oncology· 0 citations
This review synthesizes recent advances in pharmaco‐microbiomics, reframing cancer treatment in a hologenetic context, with host, tumor and microbiome acting as a tripartite entity. We comprehensively review microbiome‐mediated regulation of chemotherapeutic responses, encompassing both chemosensitization and resistance. At the molecular level, commensal microbiota enhance immunogenic cell death (ICD) and anti‐tumor immune responses, while intratumoral bacteria confer resistance through intracellular sequestration, induction of autophagy and drug inactivation (cytidine deaminase‐mediated gemcitabine degradation and β‐glucuronidase‐driven irinotecan toxicity). Our review also discusses systemic metabolic interactions including the “butyrate paradox”, competition for transporters, and microbiome‐mediated pharmacokinetics. Moving beyond microbiome profiling, we highlight functional metagenomics and resistome‐based patient stratification, complemented by AI‐based predictive modeling to predict non‐responders. In terms of translation, we outline next‐generation therapies such as engineered living medicines (ELMs), CRISPR‐bacteria for gene editing, precision bacteriophage therapy and postbiotic metabolites as precision approaches to reshape the tumor‐microbiome landscape. Finally, we present a clinical strategy combining microbiome companion diagnostics and co‐formulated “smart therapeutics” to combat multidrug resistance. This paradigm shift establishes microbiome as a predictor and therapeutic target in precision medicine.
Hailah M. Almohaimeed, Aniruddha Chatterjee, Sayani Ghosh et al.· Comprehensive Physiology· 0 citations
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