Nuclear factor κB signalling in breast cancer: mechanisms, crosstalk and therapeutic targeting.

Authors

Bavanilatha Muthiah, Raghul Rajah Santha Moorthi Rajah, Aakash Sumesh Kumar, Sudha Srikesavan, Valli Nachiyar Chandrasekaran, Kaviya Priya

Published in

Molecular biology reports. Volume 53. Issue 1. Oct 08, 2026. Epub Oct 08, 2026.

Abstract

Nuclear factor κB (NF-κB) is a context-dependent transcriptional network that integrates inflammatory, developmental, metabolic and genotoxic signals. In breast cancer, persistent or stimulus-coupled NF-κB activity can support proliferation, survival, epithelial-mesenchymal plasticity, invasion and therapy resistance, but the magnitude and biological consequences of activation differ across molecular subtypes and cellular compartments. This review critically examines canonical and non-canonical NF-κB signalling, emphasizing IKK/NEMO-dependent IκBα turnover, NIK-IKKα-dependent p100 processing, ubiquitin-dependent signalosome assembly, feedback control and context-specific NF-κB dimer composition. We then examine subtype-specific regulation in luminal A, luminal B, HER2-enriched and basal-like/triple-negative breast cancer, including crosstalk with ERα, HER2-PI3K-AKT, IL-1/TNF, RANK/RANKL and DNA-damage responses. Particular attention is given to tumour-microenvironmental signalling, macrophage heterogeneity, immune regulation, metabolic stress and treatment resistance. Evidence is explicitly separated into in vitro, in vivo, clinical-correlative and interventional levels. Therapeutic opportunities include upstream pathway inhibition, proteasome blockade, selective NIK/IKK strategies, combination approaches and emerging precision-delivery or targeted-degradation concepts. Available clinical data remain limited compared with the extensive preclinical literature, supporting biomarker-driven rather than indiscriminate NF-κB inhibition. The review identifies the major translational gaps and proposes a framework for subtype- and context-selective NF-κB targeting.

PMID:
42848272
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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