Dodonaea viscosa in Breast Cancer: Phytochemistry, Anticancer Mechanisms, and Emerging Immunotherapeutic and Translational Perspectives

Abstract

Breast cancer remains a leading cause of cancer-related mortality among women worldwide, with treatment resistance, disease heterogeneity, and therapy-associated toxicities limiting clinical outcomes. Its major clinically relevant subtypes, including oestrogen receptor-positive (ER+), human epidermal growth factor receptor 2-positive (HER2+), and triple-negative breast cancer (TNBC), differ substantially in their molecular characteristics, therapeutic targets, and treatment responses. Consequently, there is growing interest in naturally derived compounds that modulate multiple pathways involved in tumour progression and therapeutic response. Dodonaea viscosa has attracted attention because of its diverse phytochemical composition and anticancer activity. However, the contribution of its flavonoid constituents to breast cancer biology and their relevance to emerging immunotherapeutic approaches have not been comprehensively synthesized. This review critically evaluates the anticancer activity of flavonoids identified in D. viscosa, with emphasis on quercetin, kaempferol, and rutin. These compounds exhibit antioxidant, anti-inflammatory, antiproliferative, pro-apoptotic, and anti-angiogenic activities through modulation of targets implicated in breast cancer progression, including cyclooxygenase-2 (COX-2), NADPH oxidase (NOX) enzymes, vascular endothelial growth factor (VEGF), and signalling pathways associated with tumour growth, metastasis, and immune regulation. Emerging evidence also suggests that they may influence tumour-immune interactions and immune checkpoint pathways relevant to programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), highlighting potential immunotherapeutic relevance. By integrating current evidence on the phytochemistry, molecular mechanisms, and immunomodulatory properties of D. viscosa-derived flavonoids, this review provides a mechanistic and translational framework linking chemical composition to reported anticancer activity. The review identifies key gaps in mechanistic validation, pharmacokinetics, bioavailability, and clinical translation, and proposes future research priorities for evaluating D. viscosa-derived flavonoids as adjunctive candidates in breast cancer immunotherapy and precision oncology.