Hepatocellular carcinoma (HCC), a malignancy with high global morbidity and mortality, has therapeutic resistance as a major focus of both clinical and basic research. In recent years, protein post-translational modifications (PTMs), key regulators of intracellular protein function and cell signaling, play critical roles in therapeutic resistance in liver cancer. Current studies indicate that diverse PTMs—including phosphorylation, ubiquitination, acetylation, lactylation, and glycosylation—modulate liver cancer cell responses to chemotherapy, targeted therapy, immunotherapy and local therapies. This review systematically summarizes the molecular mechanisms and common pathways through which PTMs contribute to therapeutic resistance in liver cancer, explores PTM-mediated mechanism underlying tumor persistence and distant recurrence,examines how PTM-targeted strategies may reverse resistance, and discusses the challenges and prospects of these therapeutic approaches in clinical practice. By integrating current research, this review aims to provide a theoretical basis and potential targets for precision therapy of drug-resistant liver cancer, offering novel intervention targets and translational strategies to overcome therapeutic resistance in HCC.
Si-Min Feng, Jie Hu, Xiao-Xi Guo et al.· Frontiers in Immunology· 0 citations
Abstract The human gut microbiome is increasingly viewed as an active regulator of host physiology, extending beyond earlier taxonomy‐centered descriptions of a complex microbial community. Accumulating evidence supports an organ‐like conceptual framework in which the gut microbiome exhibits spatially structured organization, extensive metabolic capacity, and continuous bidirectional communication with host systems. Through the production of bioactive metabolites with endocrine‐like, immunomodulatory, and neuromodulatory properties, the microbiome contributes to metabolic, immune, and neuroendocrine regulation, thereby influencing systemic homeostasis and disease susceptibility. Recent advances in multi‐omics, spatial biology, and computational modeling are moving the field from taxonomic association toward functional interpretation, mechanistic insight, and causal inference. These approaches are beginning to reveal microbiome‐derived functional modules and host–microbe signaling networks that are shaped by host genetics, diet, medications, feeding patterns, circadian rhythms, and environmental exposures. In this review, we synthesize current mechanistic and translational evidence to conceptualize the gut microbiome as an organ‐like functional system, delineate its structural and functional organization, and propose a framework for mapping, modeling, and therapeutically targeting microbiome‐derived circuits to support precision medicine in metabolic, inflammatory, and selected gut–brain axis‐related disorders.
Yang Bi, Wei-Bin Song, Maria Glymenaki et al.· iMeta· 0 citations
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