{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:53:32Z","timestamp":1791237212995,"version":"4.1.0"},"reference-count":43,"publisher":"Radiation Research Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2026,4,23]]},"abstract":"<jats:p>Triple-negative breast cancer (TNBC) lacks actionable molecular targets, so treatment primarily relies on cytotoxic chemotherapy and radiotherapy, yet relapse, resistance, and metastasis still drives poor long-term survival. Dopamine signaling has recently been linked to tumor aggressiveness, and dopamine-receptor antagonists have shown preclinical benefit in other cancers. We therefore evaluated quetiapine (QTP), an FDA-approved DRD2\/DRD3 antagonist, as a therapeutic adjunct in TNBC. SUM159-PT, BT-549, and MDA-MB-231 cells were treated with QTP alone or combined with radiation or standard agents (doxorubicin, paclitaxel, 5-fluorouracil). Clonogenic and mammosphere assays measured proliferative and self-renewal potential. Annexin V\/propidium-iodide flow cytometry quantified apoptosis, and \u03b3-H2AX immunofluorescence tracked DNA double-strand breaks and repair kinetics. Transwell assays assessed migration of untreated bulk cells and radiation-surviving subclones. QTP significantly reduced clonogenicity and self-renewal in all TNBC models tested, both alone and in combination with radiation or chemotherapy. In apoptosis assays, QTP treatment induced a marked increase in early and late apoptotic cell populations. QTP also promoted DNA double-strand break formation and delayed repair, as indicated by persistent \u03b3-H2AX foci at 24 h after treatment. Additionally, QTP impaired the migratory capacity of both untreated and radiation-surviving cells. Combination treatments with QTP and doxorubicin produced synergistic effects, resulting in complete loss of colony-forming ability and mammosphere formation. The data presented support the repurposing of quetiapine as an adjuvant therapeutic agent alongside radiotherapy and\/or chemotherapy in TNBC. By targeting apoptosis, DNA repair, and cancer cell migration, QTP offers a novel, multi-faceted approach to improve outcomes in this high-risk breast cancer subtype.<\/jats:p>","DOI":"10.1667\/rade-25-00222.1","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T07:54:02Z","timestamp":1783410842000},"page":"55-68","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing Quetiapine as an Adjuvant Therapeutic Agent for Triple-Negative Breast Cancer"],"prefix":"10.1667","volume":"206","author":[{"given":"Ling","family":"He","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purva","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliki","family":"Ioannidis","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anoushka","family":"Kathiravan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Saki","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Pajonk","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"28","doi-asserted-by":"crossref","unstructured":"R Huang  and PK Zhou  \"Signal Transduct Target Ther.\"  6, \"DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy.\" 254 (2021)","DOI":"10.1038\/s41392-021-00648-7"},{"key":"1","doi-asserted-by":"crossref","unstructured":"RL Siegel, TB Kratzer, AN Giaquinto, et al.  \"CA Cancer J Clin.\"  75, \"Cancer statistics, 2025.\" 10 (2025)","DOI":"10.3322\/caac.21871"},{"key":"25","doi-asserted-by":"crossref","unstructured":"YC Zhou, JY Liu, J Li, et al.  \"Int J Radiat Oncol Biol Phys.\"  81, \"Ionizing radiation promotes migration and invasion of cancer cells through transforming growth factor-beta-mediated epithelial-mesenchymal transition.\" 1530 (2011)","DOI":"10.1016\/j.ijrobp.2011.06.1956"},{"key":"2","doi-asserted-by":"crossref","unstructured":"NM. 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