Adjuvant therapies by anthocyanins potentially mitigating drug resistance and metastatic disease risks in stratified breast cancers: the 3PM-conceptual innovation targeted to NF-kappaB/EMT plasticity.

Therapy resistance in breast cancer is increasingly understood as a dynamic state transition driven by inflammatory survival signaling, phenotypic plasticity, and treatment-induced adaptive rewiring rather than as a single endpoint event. Although anthocyanins and anthocyanidins are widely discussed as anticancer phytochemicals, their relevance to the therapy resistance depends on their capacity to modify defined therapy-resistant states under pharmacologically meaningful conditions. Contextually, this article critically evaluates the preclinical evidence and proposes the 3PM-guided conceptual innovation for anthocyanin- and anthocyanidin-linked drug sensitization in therapy-resistant breast cancers, using specifically the NF-κB/EMT crosstalk as a functional lens. To this end, NF-κB/EMT signaling as the proposed target, per strong scientific evidence, is involved in pathways considered central for the phenotype-specific epigenetic regulation of health risks, malignant transformation, development of metastatic disease and therapy resistance. Finally, patient phenotyping and stratification, targeted risk mitigation and treatments tailored to individualized patient profiles are considered essential pillars for improved individual outcomes in the 3PM-guided paradigm.