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Publications

Journal Article Review Epublish

PubMed: 40790759 DOI: 10.1186/s13046-025-03500-w

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

J Exp Clin Cancer Res 44(1):234

Authors: Manon Desgres, Melis Poyraz, Buse Sari, François P Duhoux, Cédric van Marcke, Cyril Corbet

Affiliations

  • Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, Brussels, B-1200, Belgium.
  • Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, Brussels, B-1200, Belgium.
  • Pole of Medical Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Brussels, Belgium.
  • Department of Medical Oncology, Institut Roi Albert II, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
  • Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, Brussels, B-1200, Belgium.
  • WEL Research Institute, avenue Pasteur 6, Wavre, B-1300, Belgium.

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.

MeSH

Breast Neoplasms, Neoplasms, Drug Therapy, Breast, Therapeutics, Chemotherapy