Flavonol-mediated modulation of angiogenesis-related microRNAs in breast cancer: a narrative synthesis of current evidence and knowledge gaps

Abstract

Angiogenesis is essential for breast cancer progression and metastasis; however, the clinical impact of vascular endothelial growth factor (VEGF)-targeted therapies remains limited due to adaptive resistance and activation of compensatory angiogenic pathways. Angiogenesis-regulating microRNAs (angiomiRs) act as upstream modulators of both VEGF-dependent and VEGF-independent signaling networks contributing to vascular plasticity, immune evasion, and therapeutic escape. Dietary flavonols such as kaempferol, myricetin, and quercetin have demonstrated anti-angiogenic activity in preclinical models, yet their mechanistic interaction with angiomiR-mediated regulation in breast cancer remains poorly characterized. This narrative review critically evaluates evidence identified through structured searches of Google Scholar, PubMed, Scopus, and Web of Science (2010-2026). We synthesize mechanistic and translational findings linking flavonols to microRNA-associated regulation of hypoxia signaling, endothelial activation, extracellular vesicle communication, and vascular normalization. Available evidence indicates that flavonols may influence angiogenic pathways both directly, by inhibiting key signaling cascades, and indirectly, through modulation of non-coding RNA networks. Despite these insights, experimental validation of specific flavonol-angiomiR interactions in breast cancer remains limited. AngiomiR modulation by flavonols, therefore, represents a mechanistically grounded but predominantly preclinical concept that warrants further translational investigation to clarify its therapeutic relevance and potential applications within precision oncology in breast cancer.