Targeting the gut and tumor microbiome in cancer treatment resistance.

IF 5 2区 生物学 Q2 CELL BIOLOGY
Sona Ciernikova, Aneta Sevcikova, Michal Mego
{"title":"Targeting the gut and tumor microbiome in cancer treatment resistance.","authors":"Sona Ciernikova, Aneta Sevcikova, Michal Mego","doi":"10.1152/ajpcell.00201.2024","DOIUrl":null,"url":null,"abstract":"<p><p>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 microenvironments 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 proapoptotic 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 pretreatment 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.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1433-C1450"},"PeriodicalIF":5.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Cell physiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1152/ajpcell.00201.2024","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

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 microenvironments 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 proapoptotic 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 pretreatment 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.

在抗癌过程中瞄准肠道和肿瘤微生物组。
抗药性是肿瘤学面临的一项重大挑战,在各种治疗方法中都会出现。最近,动物模型和越来越多的临床试验凸显了肠道和肿瘤微生物组对治疗反应的重要影响。肠道微生物组有助于癌症的发生、发展和远处转移。此外,肿瘤相关微生物群被认为是影响肿瘤微环境和调节局部免疫过程的关键因素。耐人寻味的是,许多研究已成功鉴定出肠道和肿瘤微生物群中的病原体,这些病原体可能与对不同治疗方式的不良反应有关。存在特定微生物的不利微生物组成通过几种机制参与癌症的抗药性和进展,包括致癌途径的上调、巨噬细胞极化重编程、化疗化合物的代谢、自噬途径调节、DNA 损伤修复增强、促凋亡级联失活,以及细菌分泌细胞外囊泡,促进转移级联过程。有针对性地消除特定的瘤内细菌似乎能增强治疗反应。然而,广谱抗生素预处理大多与肠道菌群失调和多样性降低导致的疗效降低有关。越来越多的证据支持通过益生菌和粪便微生物群移植来调节微生物群,以改善肠道菌群失调和增加微生物多样性,从而提高疗效,同时减轻不良反应。在这种情况下,进一步研究确定临床相关的微生物组特征,然后采取微生物组靶向策略,是克服难治性患者免疫疗法和化疗耐药性、改善其预后的一种有希望的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信