Breast cancer progression and therapeutic response are profoundly influenced by tumor immune interactions, yet the molecular regulators linking cell death pathways with immune modulation remain incompletely understood. Pyroptosis, a gasdermin-mediated inflammatory form of programmed cell death, has emerged as a key determinant of tumor immunity, while long non-coding RNAs are increasingly recognized as critical upstream regulators of cancer signaling. Recent transcriptomic analyses have identified numerous pyroptosis-associated lncRNAs and generated prognostic signatures that stratify patients into distinct risk groups with significantly different survival outcomes. These signatures are closely associated with the tumor immune microenvironment: low-risk tumors exhibit increased infiltration of CD8+ T cells, NK cells, and B cells, together with elevated immune checkpoint expression, whereas high-risk tumors display immunosuppressive features, including M2 macrophage enrichment and higher tumor mutation burden. Mechanistic studies demonstrate that lncRNAs regulate pyroptosis through inflammasome activation, gasdermin-mediated signaling, and epigenetic modulation, thereby influencing tumor growth, metastasis, and therapeutic resistance. Despite these advances, clinical translation remains limited by dependence on retrospective transcriptomic datasets, insufficient mechanistic validation, lack of standardized assays, and scarce prospective clinical evidence. pyroptosis-associated lncRNAs represent a promising link between tumor progression and immune regulation, with considerable potential as prognostic biomarkers and therapeutic targets in breast cancer.
Gastrointestinal (GI) cancers, including colorectal, gastric, pancreatic, hepatocellular, and esophageal malignancies, remain a leading cause of cancer-related mortality worldwide. Emerging evidence identifies the gut microbiome as a critical regulator of GI carcinogenesis, influencing tumor initiation, immune evasion, therapeutic response, and clinical outcomes through inflammation, genotoxicity, metabolic reprogramming, and epithelial barrier disruption. Importantly, biological rationale, clinical evidence, and translational opportunities differ across GI tumor types. Specific taxa, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, and Helicobacter pylori, exhibit tumor-specific oncogenic roles with causal evidence ranging from associative to guideline-validated. Microbiome-based biomarkers, including composite multi-taxon models and signatures predictive of immune checkpoint inhibitor response, are evaluated using a four-tier framework (preclinical, associative, near-clinical, and validated). Microbiome-targeted therapies, including probiotics, fecal microbiota transplantation, dietary modulation, and engineered microbial therapeutics, are critically appraised according to clinical evidence and translational readiness. Advances in spatial microbiomics, single-cell analysis, multi-omics, and artificial intelligence may further accelerate microbiome-based precision oncology. This review provides a translationally stratified synthesis of microbiome-GI cancer interactions and their implications for precision oncology.
Hormesis is a biphasic dose-response, where mild stress triggers adaptive defense responses that increase cellular resilience. The hormesis is now recognized as a core concept with applications in toxicology, metabolism, aging, and evolutionary biology. A historical review, evolutionary explanations, and recent molecular insights led to the concept of hormesis as an anticipatory, "predict-and-prepare" strategy that allows organisms to adapt to changing conditions are addressed. The mitohormesis, autophagy, xenohormesis, epigenetic remodeling, and their interdependence with signaling pathways (Nrf2-KEAP1, AMPK-SIRT1, NF-κB, and heat-shock response). The stress-induced reversal of differentiation in basal metazoans also defy the irreversible aging concept demonstrate conservative plasticity programs. The relevance of translational research using toxin-derived therapeutics and lifestyle-based hormetic interventions are discussed, including challenges of the hormetic zone, inter-individual variability, and bioactivity cliffs. The future scope of integrating AI and ML into nonlinear modeling of precise hormetic dosing, with considerable applications in aging, regenerative medicine, and precision therapeutics.
