{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:49:27Z","timestamp":1791524967410,"version":"4.3.4"},"reference-count":101,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001325","name":"Cancer Association of South Africa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Breast cancer remains a leading cause of cancer\u2010related mortality among women worldwide, with treatment resistance, disease heterogeneity, and therapy\u2010associated toxicities limiting clinical outcomes. Its major clinically relevant subtypes, including oestrogen receptor\u2010positive (ER+), human epidermal growth factor receptor 2\u2010positive (HER2+), and triple\u2010negative 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.\n \n Dodonaea viscosa<\/jats:italic>\n <\/jats:styled-content>\n 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\n \n D. viscosa<\/jats:italic>\n <\/jats:styled-content>\n , with emphasis on quercetin, kaempferol, and rutin. These compounds exhibit antioxidant, anti\u2010inflammatory, antiproliferative, pro\u2010apoptotic, and anti\u2010angiogenic activities through modulation of targets implicated in breast cancer progression, including cyclooxygenase\u20102 (COX\u20102), 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\u2010immune interactions and immune checkpoint pathways relevant to programmed cell death protein\u20101 (PD\u20101) and cytotoxic T\u2010lymphocyte\u2010associated protein\u20104 (CTLA\u20104), highlighting potential immunotherapeutic relevance. By integrating current evidence on the phytochemistry, molecular mechanisms, and immunomodulatory properties of\n \n D. viscosa<\/jats:italic>\n <\/jats:styled-content>\n \u2010derived 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\n \n D. viscosa<\/jats:italic>\n <\/jats:styled-content>\n \u2010derived flavonoids as adjunctive candidates in breast cancer immunotherapy and precision oncology.\n <\/jats:p>","DOI":"10.1002\/cam4.72240","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:55:56Z","timestamp":1791521756000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dodonaea viscosa<\/i>\n in Breast Cancer: Phytochemistry, Anticancer Mechanisms, and Emerging Immunotherapeutic and Translational Perspectives"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-4115","authenticated-orcid":false,"given":"Nireshini","family":"Reddy","sequence":"first","affiliation":[{"name":"Department of Physiological Sciences, Faculty of Science Stellenbosch University Stellenbosch South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine H.","family":"Kaschula","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Polymer Science, Faculty of Science Stellenbosch University Stellenbosch South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1507-251X","authenticated-orcid":false,"given":"Nokwanda P.","family":"Makunga","sequence":"additional","affiliation":[{"name":"Dept of Botany and Zoology, Faculty of Science Stellenbosch University Stellenbosch South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-3321","authenticated-orcid":false,"given":"Willem Jacobus","family":"Perold","sequence":"additional","affiliation":[{"name":"Department of Electrical and Electronic Engineering, Faculty of Engineering Stellenbosch University Stellenbosch South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5637-5368","authenticated-orcid":false,"given":"Sanjeev","family":"Rambharose","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, Faculty of Science Stellenbosch University Stellenbosch South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1469-0148","authenticated-orcid":false,"given":"Anna\u2010Mart","family":"Engelbrecht","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, Faculty of Science Stellenbosch University Stellenbosch South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"issue":"10","key":"e_1_2_13_3_1","first-page":"2929","article-title":"Breast Cancer Intrinsic Subtype Classification, Clinical Use and Future Trends","volume":"5","author":"Dai X.","year":"2015","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41523\u2010022\u201000468\u20100"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102699.2009.02176.x"},{"issue":"1","key":"e_1_2_13_6_1","first-page":"97","article-title":"Dodonaea viscosa\n Linn. 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