The gut microbiota significantly influences hepatobiliary cancer therapeutics. Growing evidence indicates that shifts in the gut microbial ecosystem are hallmarks of hepatocellular carcinoma and cholangiocarcinoma, strongly correlating with tumor development, therapeutic resistance, and patient survival. The composition of gut microbiota has emerged as a biomarker associated with treatment outcomes across various modalities, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Beneficial bacterial communities enhance antitumor immunity, while pathogenic taxa are linked to reduced therapeutic efficacy. Multi-omics analyses have identified microbial metabolite signatures, such as short-chain fatty acids and bile acids, as potential targets for boosting antitumor responses. This review highlights the transformative potential of leveraging the gut microbiota to enhance precision oncology in hepatobiliary cancer. Future directions should prioritize personalized microbiota modulation approaches, combinatorial therapies targeting gut-liver axis crosstalk, and large-scale validation of microbial biomarkers across diverse populations.
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Hepatocellular carcinoma (HCC) is a highly lethal cancer due to its aggressive nature and poor prognosis. Adenosine, a key metabolic regulator in the tumor microenvironment (TME), plays a crucial role in cancer progression. In this review, we first described adenosine triphosphate adenosine metabolism in the TME and summarized its effects on tumor growth, immune suppression, angiogenesis, and metastasis in HCC. Given the limited number of clinical studies on adenosine signaling in HCC, we conducted LASSO-Cox analysis using the TCGA-LIHC cohort to develop a prognostic risk model composed of eight adenosine signaling-related genes. This model stratified the patients into low- and high-risk groups, with Kaplan-Meier survival analysis revealing poorer overall survival in the high-risk group. Additionally, differential gene expression analysis between the two groups identified 24 enriched signaling pathways for further investigation. Immune infiltration and single cell RNA-seq analyses revealed a correlation between adenosine and immunosuppressive activity in the TME, with a particularly strong association observed in macrophages, dendritic cells, and monocytes. Finally, we provided an overview of the advancements of antagonists that target adenosine receptors’ progress in both preclinical research and clinical trials. In conclusion, this review aims to deepen our understanding of the biological role of adenosine and highlights emerging therapeutic strategies that may improve treatment outcomes for HCC.
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