失调
微生物群
生物
肠道菌群
肿瘤微环境
癌症研究
免疫系统
殖民抵抗
癌症
免疫学
生物信息学
微生物学
抗生素
遗传学
作者
Sona Ciernikova,Aneta Sevcikova,Michal Mego
出处
期刊:American Journal of Physiology-cell Physiology
[American Physiological Society]
日期:2024-10-22
标识
DOI:10.1152/ajpcell.00201.2024
摘要
Therapy resistance represents a significant challenge in oncology, occurring in various therapeutic approaches. Recently, animal models and an increasing set of clinical trials highlight the crucial impact of the gut and tumor microbiome on treatment response. The intestinal microbiome contributes to cancer initiation, progression, and formation of distant metastasis. In addition, tumor-associated microbiota is considered a critical player in influencing tumor microenvironment and regulating local immune processes. Intriguingly, numerous studies have successfully identified pathogens within the gut and tumor microbiome that might be linked to a poor response to different therapeutic modalities. The unfavorable microbial composition with the presence of specific microbes participates in cancer resistance and progression via several mechanisms, including upregulation of oncogenic pathways, macrophage polarization reprogramming, metabolism of chemotherapeutic compounds, autophagy pathway modulation, enhanced DNA damage repair, inactivation of a pro-apoptotic cascade, and bacterial secretion of extracellular vesicles, promoting the processes in the metastatic cascade. Targeted elimination of specific intratumoral bacteria appears to enhance treatment response. However, broad-spectrum antibiotic pre-treatment is mostly connected to reduced efficacy due to gut dysbiosis and lower diversity. Mounting evidence supports the potential of microbiota modulation by probiotics and fecal microbiota transplantation to improve intestinal dysbiosis and increase microbial diversity, leading to enhanced treatment efficacy while mitigating adverse effects. In this context, further research concerning the identification of clinically relevant microbiome signatures followed by microbiota-targeted strategies presents a promising approach to overcoming immunotherapy and chemotherapy resistance in refractory patients, improving their outcomes.
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