Resistance to neoadjuvant chemotherapy in breast cancers: a metabolic perspective.

IF 12.8 1区 医学 Q1 ONCOLOGY
Manon Desgres, Melis Poyraz, Buse Sari, François P Duhoux, Cédric van Marcke, Cyril Corbet
{"title":"Resistance to neoadjuvant chemotherapy in breast cancers: a metabolic perspective.","authors":"Manon Desgres, Melis Poyraz, Buse Sari, François P Duhoux, Cédric van Marcke, Cyril Corbet","doi":"10.1186/s13046-025-03500-w","DOIUrl":null,"url":null,"abstract":"<p><p>Neoadjuvant chemotherapy (NAC) is a cornerstone in the treatment of early-stage high-risk breast cancers (BC), particularly in triple-negative, HER2-positive, and selected hormone receptor-positive subtypes. However, its effectiveness is frequently hindered by intrinsic or acquired resistance, resulting in a significant residual cancer burden (RCB) in more than half of patients. Despite extensive genomic profiling, reliable predictive biomarkers for treatment response remain limited, impeding the development of personalized therapeutic strategies. Emerging evidence highlights tumor metabolic reprogramming as a key non-genetic mechanism contributing to NAC resistance. In this review, we critically examine current advances in metabolic imaging and metabolomics as tools to predict NAC response in BC. We also discuss the role of the tumor microenvironment (TME), including hypoxia and acidosis, in shaping metabolic plasticity and fostering treatment resistance. Furthermore, we explore novel therapeutic strategies targeting metabolic pathways, ranging from enzyme inhibition to dietary interventions, and the use of advanced preclinical models. Together, these insights offer a metabolic framework for overcoming NAC resistance and advancing precision oncology in early-stage BC.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"44 1","pages":"234"},"PeriodicalIF":12.8000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12337530/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Experimental & Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13046-025-03500-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Neoadjuvant chemotherapy (NAC) is a cornerstone in the treatment of early-stage high-risk breast cancers (BC), particularly in triple-negative, HER2-positive, and selected hormone receptor-positive subtypes. However, its effectiveness is frequently hindered by intrinsic or acquired resistance, resulting in a significant residual cancer burden (RCB) in more than half of patients. Despite extensive genomic profiling, reliable predictive biomarkers for treatment response remain limited, impeding the development of personalized therapeutic strategies. Emerging evidence highlights tumor metabolic reprogramming as a key non-genetic mechanism contributing to NAC resistance. In this review, we critically examine current advances in metabolic imaging and metabolomics as tools to predict NAC response in BC. We also discuss the role of the tumor microenvironment (TME), including hypoxia and acidosis, in shaping metabolic plasticity and fostering treatment resistance. Furthermore, we explore novel therapeutic strategies targeting metabolic pathways, ranging from enzyme inhibition to dietary interventions, and the use of advanced preclinical models. Together, these insights offer a metabolic framework for overcoming NAC resistance and advancing precision oncology in early-stage BC.

乳腺癌对新辅助化疗的耐药性:代谢的观点。
新辅助化疗(NAC)是早期高危乳腺癌(BC)治疗的基石,特别是在三阴性、her2阳性和选定的激素受体阳性亚型中。然而,其有效性经常受到内在或获得性耐药的阻碍,导致超过一半的患者存在显著的残余癌症负担(RCB)。尽管广泛的基因组分析,可靠的预测治疗反应的生物标志物仍然有限,阻碍了个性化治疗策略的发展。新出现的证据强调肿瘤代谢重编程是促成NAC耐药的关键非遗传机制。在这篇综述中,我们批判性地研究了代谢成像和代谢组学作为预测BC患者NAC反应的工具的最新进展。我们还讨论了肿瘤微环境(TME),包括缺氧和酸中毒,在形成代谢可塑性和促进治疗抵抗中的作用。此外,我们探索针对代谢途径的新治疗策略,从酶抑制到饮食干预,以及使用先进的临床前模型。总之,这些见解为克服NAC耐药和推进早期BC的精确肿瘤学提供了一个代谢框架。
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
18.20
自引率
1.80%
发文量
333
审稿时长
1 months
期刊介绍: The Journal of Experimental & Clinical Cancer Research is an esteemed peer-reviewed publication that focuses on cancer research, encompassing everything from fundamental discoveries to practical applications. We welcome submissions that showcase groundbreaking advancements in the field of cancer research, especially those that bridge the gap between laboratory findings and clinical implementation. Our goal is to foster a deeper understanding of cancer, improve prevention and detection strategies, facilitate accurate diagnosis, and enhance treatment options. We are particularly interested in manuscripts that shed light on the mechanisms behind the development and progression of cancer, including metastasis. Additionally, we encourage submissions that explore molecular alterations or biomarkers that can help predict the efficacy of different treatments or identify drug resistance. Translational research related to targeted therapies, personalized medicine, tumor immunotherapy, and innovative approaches applicable to clinical investigations are also of great interest to us. We provide a platform for the dissemination of large-scale molecular characterizations of human tumors and encourage researchers to share their insights, discoveries, and methodologies with the wider scientific community. By publishing high-quality research articles, reviews, and commentaries, the Journal of Experimental & Clinical Cancer Research strives to contribute to the continuous improvement of cancer care and make a meaningful impact on patients' lives.
×
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:604180095
Book学术官方微信