{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:44:38Z","timestamp":1792586678299,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol Toxicol"],"DOI":"10.1186\/s40360-026-01198-w","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:24:35Z","timestamp":1792509875000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["When drug repurposing backfires: antagonistic effects of ivermectin on cisplatin therapy in oral cancer"],"prefix":"10.1186","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4868-4315","authenticated-orcid":false,"given":"Rana","family":"Tantawy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shereen Nader","family":"Raafat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"El-Gawish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Ghalwash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"issue":"6","key":"1198_CR1","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.ajoms.2020.06.013","volume":"32","author":"DM Ghalwash","year":"2020","unstructured":"Ghalwash DM. Diagnostic and prognostic value of salivary biomarkers in oral cancer and precancer: Review article. J Oral Maxillofacial Surg Med Pathol. 2020;32(6):538\u201343. https:\/\/doi.org\/10.1016\/j.ajoms.2020.06.013.","journal-title":"J Oral Maxillofacial Surg Med Pathol"},{"key":"1198_CR2","doi-asserted-by":"publisher","first-page":"825266","DOI":"10.3389\/fphar.2022.825266","volume":"13","author":"P Kumari","year":"2022","unstructured":"Kumari P, Debta P, Dixit A. Oral Potentially Malignant Disorders: Etiology, Pathogenesis, and Transformation Into Oral Cancer. Front Pharmacol. 2022;13:825266.","journal-title":"Front Pharmacol"},{"issue":"1","key":"1198_CR3","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1111\/PRD.12567","volume":"96","author":"DF Kinane","year":"2024","unstructured":"Kinane DF, Gabert J, Xynopoulos G, Guzeldemir-Akcakanat E. Strategic approaches in oral squamous cell carcinoma diagnostics using liquid biopsy. Periodontol 2000. 2024;96(1):316\u201328. https:\/\/doi.org\/10.1111\/PRD.12567.","journal-title":"Periodontol 2000"},{"issue":"4","key":"1198_CR4","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1111\/odi.15182","volume":"31","author":"FM Zahran","year":"2025","unstructured":"Zahran FM, Elsaadany B, Azab NA, El-Gawish A, Ghalwash D. Dysplasia in Oral Lichen Planus in a Sample of Egyptians Attending 2 Tertiary Care Centers in Cairo. Oral Dis. 2025;31(4):1386\u20137. https:\/\/doi.org\/10.1111\/odi.15182.","journal-title":"Oral Dis"},{"key":"1198_CR5","doi-asserted-by":"publisher","unstructured":"Ghalwash D, Zahran fatheya. Oral cancer awareness among dentists: what is missing? A cross-sectional study. J Egypt Natl Cancer Inst. 2025;37(1). https:\/\/doi.org\/10.1186\/s43046-025-00290-2.","DOI":"10.1186\/s43046-025-00290-2"},{"key":"1198_CR6","doi-asserted-by":"publisher","unstructured":"Ebrahimi R, Masouri MM, Razeghian I, Azad G, Nejadghaderi SA. Lip, Oral Cavity, and pharyngeal cancers: global epidemiology, risk factors, and prevention: a narrative review. Health Sci Rep. 2025;8(10). https:\/\/doi.org\/10.1002\/HSR2.71289.","DOI":"10.1002\/HSR2.71289"},{"key":"1198_CR7","unstructured":"Ghalwash D, zahran fatheya, Gaaly K, Shaker O, Elfoll H, Ghalwash D, zahran K, Shaker O, Elfoll H. (2012). The diagnostic and prognostic value of salivary scd44 level determination in oral malignant and potentially premalignant lesions. Dentistry. https:\/\/buescholar.bue.edu.eg\/dentistry\/255"},{"key":"1198_CR8","doi-asserted-by":"publisher","first-page":"100678","DOI":"10.1016\/J.OOR.2024.100678","volume":"12","author":"S Ramachandran","year":"2024","unstructured":"Ramachandran S. Oral cancer: Recent breakthroughs in pathology and therapeutic approaches. Oral Oncol Rep. 2024;12:100678. https:\/\/doi.org\/10.1016\/J.OOR.2024.100678.","journal-title":"Oral Oncol Rep"},{"key":"1198_CR9","doi-asserted-by":"publisher","unstructured":"Mortensen ACL, Mohajershojai T, Hariri M, Pettersson M, Spiegelberg D. Overcoming limitations of cisplatin therapy by additional treatment With the HSP90 inhibitor onalespib. Front Oncol. 2020;10. https:\/\/doi.org\/10.3389\/FONC.2020.532285.","DOI":"10.3389\/FONC.2020.532285"},{"issue":"8","key":"1198_CR10","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.3390\/MOLECULES27082466","volume":"27","author":"D Tsvetkova","year":"2022","unstructured":"Tsvetkova D, Ivanova S. Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases. Molecules. 2022;27(8):2466. https:\/\/doi.org\/10.3390\/MOLECULES27082466.","journal-title":"Molecules"},{"key":"1198_CR11","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","volume":"740","author":"S Dasari","year":"2014","unstructured":"Dasari S, Bernard Tchounwou P. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. 2014;740:364\u201378. https:\/\/doi.org\/10.1016\/j.ejphar.2014.07.025.","journal-title":"Eur J Pharmacol"},{"key":"1198_CR12","doi-asserted-by":"publisher","unstructured":"Brown A, Kumar S, Tchounwou PB. (2019). Cisplatin-based chemotherapy of human Cancers. J Cancer Sci Therapy. 11(4):97\u2013103. https:\/\/doi.org\/10.4172\/1948-5956.1000592. PMC7059781.","DOI":"10.4172\/1948-5956.1000592"},{"key":"1198_CR13","doi-asserted-by":"publisher","first-page":"106939","DOI":"10.1016\/J.EJPS.2024.106939","volume":"203","author":"EA Elmorsy","year":"2024","unstructured":"Elmorsy EA, Saber S, Hamad RS, Abdel-Reheim MA, El-kott AF, AlShehri MA, Morsy K, Salama SA, Youssef ME. Advances in understanding cisplatin-induced toxicity: Molecular mechanisms and protective strategies. Eur J Pharm Sci. 2024;203:106939. https:\/\/doi.org\/10.1016\/J.EJPS.2024.106939.","journal-title":"Eur J Pharm Sci"},{"key":"1198_CR14","doi-asserted-by":"publisher","unstructured":"Ghosh S. Cisplatin: The first metal based anticancer drug. Bioorg Chem. 2019;88. https:\/\/doi.org\/10.1016\/j.bioorg.2019.102925.","DOI":"10.1016\/j.bioorg.2019.102925"},{"key":"1198_CR15","doi-asserted-by":"publisher","first-page":"2747","DOI":"10.2147\/DDDT.S308973","volume":"15","author":"H Huang","year":"2021","unstructured":"Huang H, He Q, Guo B, Xu X, Wu Y, Li X. Progress in Redirecting Antiparasitic Drugs for Cancer Treatment. Drug Des Devel Ther. 2021;15:2747. https:\/\/doi.org\/10.2147\/DDDT.S308973.","journal-title":"Drug Des Devel Ther"},{"key":"1198_CR16","doi-asserted-by":"publisher","unstructured":"Tang M, Hu X, Wang Y, Yao X, Zhang W, Yu C, Cheng F, Li J, Fang Q. (2021). Ivermectin, a potential anticancer drug derived from an antiparasitic drug. In Pharmacological Research (Vol. 163). Academic Press. https:\/\/doi.org\/10.1016\/j.phrs.2020.105207.","DOI":"10.1016\/j.phrs.2020.105207"},{"key":"1198_CR17","doi-asserted-by":"publisher","unstructured":"Diao H, Cheng N, Zhao Y, Xu H, Dong H, Thamm DH, Zhang D, Lin D. Ivermectin inhibits canine mammary tumor growth by regulating cell cycle progression and WNT signaling. BMC Vet Res. 2019;15(1). https:\/\/doi.org\/10.1186\/S12917-019-2026-2.","DOI":"10.1186\/S12917-019-2026-2"},{"issue":"12","key":"1198_CR18","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1080\/15548627.2016.1231494","volume":"12","author":"K Wang","year":"2016","unstructured":"Wang K, Gao W, Dou Q, Chen H, Li Q, Nice EC, Huang C. Ivermectin induces PAK1-mediated cytostatic autophagy in breast cancer. Autophagy. 2016;12(12):2498. https:\/\/doi.org\/10.1080\/15548627.2016.1231494.","journal-title":"Autophagy"},{"issue":"23","key":"1198_CR19","doi-asserted-by":"publisher","first-page":"38022","DOI":"10.18632\/ONCOTARGET.16723","volume":"8","author":"RB Mokhtari","year":"2017","unstructured":"Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, Yeger H, Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, Yeger H. Combination therapy in combating cancer. Oncotarget. 2017;8(23):38022\u201343. https:\/\/doi.org\/10.18632\/ONCOTARGET.16723.","journal-title":"Oncotarget"},{"key":"1198_CR20","doi-asserted-by":"publisher","unstructured":"Xia Y, Sun M, Huang H, Jin WL. (2024). Drug repurposing for cancer therapy. Signal transduction and targeted therapy 2024;9(1):92. https:\/\/doi.org\/10.1038\/s41392-024-01808-1.","DOI":"10.1038\/s41392-024-01808-1"},{"key":"1198_CR21","doi-asserted-by":"publisher","unstructured":"Raafat SN, El Wahed SA, Badawi NM, Saber MM, Abdollah MRA. Enhancing the anticancer potential of metformin: fabrication of efficient nanospanlastics, in vitro cytotoxic studies on HEP-2 cells and reactome enhanced pathway analysis. Int J Pharmaceutics: X. 2023;6. https:\/\/doi.org\/10.1016\/j.ijpx.2023.100215.","DOI":"10.1016\/j.ijpx.2023.100215"},{"key":"1198_CR22","doi-asserted-by":"publisher","unstructured":"Mehraj U, Mir IA, Hussain M, ul Alkhanani, Wani M, Mir NA, MA. Adapalene and doxorubicin synergistically promote apoptosis of TNBC cells by hyperactivation of the ERK1\/2 pathway through ROS induction. Front Oncol. 2022;12. https:\/\/doi.org\/10.3389\/fonc.2022.938052.","DOI":"10.3389\/fonc.2022.938052"},{"key":"1198_CR23","doi-asserted-by":"publisher","first-page":"2990670","DOI":"10.1155\/2024\/2990670","volume":"2024","author":"SS Mohamed","year":"2024","unstructured":"Mohamed SS, Zaki HF, Raafat SN. The Effect of Clopidogrel and Ticagrelor on Human Adipose Mesenchymal Stem Cell Osteogenic Differentiation Potential: In Vitro Comparative Study. Adv Pharmacol Pharm Sci. 2024;2024:2990670. https:\/\/doi.org\/10.1155\/2024\/2990670.","journal-title":"Adv Pharmacol Pharm Sci"},{"key":"1198_CR24","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/978-1-61779-867-2_20","volume":"889","author":"TE Tipple","year":"2012","unstructured":"Tipple TE, Rogers LK. Methods for the determination of plasma or tissue glutathione levels. Methods Mol Biol. 2012;889:315\u201324. https:\/\/doi.org\/10.1007\/978-1-61779-867-2_20.","journal-title":"Methods Mol Biol"},{"key":"1198_CR25","doi-asserted-by":"publisher","unstructured":"Tantawy R, Raafat SN, El-Gawish A, Ghalwash D. Synergistic potential of Ivermectin and doxorubicin in oral squamous cell carcinoma: an in vitro investigation. BMC Pharmacol Toxicol.2025. https:\/\/doi.org\/10.1186\/S40360-025-01053-4.","DOI":"10.1186\/S40360-025-01053-4"},{"key":"1198_CR26","doi-asserted-by":"publisher","unstructured":"Kleih M, B\u00f6pple K, Dong M, Gai\u00dfler A, Heine S, Olayioye MA, Aulitzky WE, Essmann F. Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells. Cell Death Dis. 2019;10(11). https:\/\/doi.org\/10.1038\/s41419-019-2081-4.","DOI":"10.1038\/s41419-019-2081-4"},{"issue":"6","key":"1198_CR27","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1007\/S00280-020-04041-Z","volume":"85","author":"M Juarez","year":"2020","unstructured":"Juarez M, Schcolnik-Cabrera A, Dominguez-Gomez G, Chavez-Blanco A, Diaz-Chavez J, Duenas-Gonzalez A. Antitumor effects of ivermectin at clinically feasible concentrations support its clinical development as a repositioned cancer drug. Cancer Chemother Pharmacol. 2020;85(6):1153\u201363. https:\/\/doi.org\/10.1007\/S00280-020-04041-Z.","journal-title":"Cancer Chemother Pharmacol"},{"key":"1198_CR28","doi-asserted-by":"publisher","unstructured":"Zhang X, Qin T, Zhu Z, Hong F, Xu Y, Zhang, Xiongjie, Xu X, Ma A. (2020). Ivermectin augments the in vitro and in vivo efficacy of cisplatin in epithelial ovarian cancer by suppressing Akt\/mTOR signaling. American Journal of the Medical Sciences, 359(2), 123\u2013129. https:\/\/doi.org\/10.1016\/j.amjms.2019.11.001","DOI":"10.1016\/j.amjms.2019.11.001"},{"key":"1198_CR29","doi-asserted-by":"publisher","unstructured":"Corsello, S. M., Nagari, R. T., Spangler, R. D., Rossen, J., Kocak, M., Bryan, J.G., Humeidi, R., Peck, D., Wu, X., Tang, A. A., Wang, V. M., Bender, S. A., Lemire,E., Narayan, R., Montgomery, P., Ben-David, U., Garvie, C. W., Chen, Y., Rees, M.G., \u2026 Golub, T. R. Discovering the anticancer potential of non-oncology drugs by systematic viability profiling. Nature Cancer 2020; 1(2), 235\u2013248. https:\/\/doi.org\/10.1038\/s43018-019-0018-6.","DOI":"10.1038\/s43018-019-0018-6"},{"issue":"8","key":"1198_CR30","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1631\/JZUS.B2200385","volume":"24","author":"MA Abd-Elmawla","year":"2023","unstructured":"Abd-Elmawla MA, Ghaiad HR, Gad ES, Ahmed KA, Abdelmonem M. Suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis. J Zhejiang University-SCIENCE B 2023. 2023;24(8):8. https:\/\/doi.org\/10.1631\/JZUS.B2200385.","journal-title":"J Zhejiang University-SCIENCE B 2023"},{"key":"1198_CR31","doi-asserted-by":"publisher","first-page":"e478s","DOI":"10.6061\/clinics\/2018\/e478s","volume":"73","author":"CRR Rocha","year":"2018","unstructured":"Rocha CRR, Silva MM, Quinet A, Cabral-Neto JB, Menck CFM. DNA repair pathways and cisplatin resistance: an intimate relationship. Clinics. 2018;73:e478s. https:\/\/doi.org\/10.6061\/clinics\/2018\/e478s.","journal-title":"Clinics"},{"key":"1198_CR32","doi-asserted-by":"publisher","unstructured":"Psyrri A, Gkotzamanidou M, Papaxoinis G, Krikoni L, Economopoulou P, Kotsantis I, Anastasiou M, Souliotis VL. The DNA damage response network in the treatment of head and neck squamous cell carcinoma. ESMO Open. 2021;6(2). https:\/\/doi.org\/10.1016\/j.esmoop.2021.100075.","DOI":"10.1016\/j.esmoop.2021.100075"},{"key":"1198_CR33","doi-asserted-by":"publisher","unstructured":"Butkiewicz D, Krze\u015bniak M, Gdowicz-K\u0142osok A, Sk\u0142adowski K, Rutkowski T. DNA double-strand break response and repair gene polymorphisms may influence therapy results and prognosis in head and neck cancer patients. Cancers. 2023;15(20). https:\/\/doi.org\/10.3390\/cancers15204972.","DOI":"10.3390\/cancers15204972"},{"key":"1198_CR34","doi-asserted-by":"publisher","unstructured":"Ma Y, Xu X, Wu H, Li C, Zhong P, Liu Z, Ma C, Liu W, Wang C, Zhang Y, Wang J. Ivermectin contributes to attenuating the severity of acute lung injury in mice. Biomed Pharmacotherapy. 2022;155. https:\/\/doi.org\/10.1016\/j.biopha.2022.113706.","DOI":"10.1016\/j.biopha.2022.113706"},{"key":"1198_CR35","doi-asserted-by":"publisher","unstructured":"Dong XQ, Chu LK, Cao X, Xiong QW, Mao YM, Chen CH, Bi YL, Liu J, Yan XM. Glutathione metabolism rewiring protects renal tubule cells against cisplatin-induced apoptosis and ferroptosis. Redox Report: Commun Free Radical Res. 2023;28(1). https:\/\/doi.org\/10.1080\/13510002.2022.2152607.","DOI":"10.1080\/13510002.2022.2152607"},{"key":"1198_CR36","doi-asserted-by":"publisher","unstructured":"Katani\u0107 Stankovi\u0107 JS, Selakovi\u0107 D, Rosi\u0107 G. Oxidative damage as a fundament of systemic toxicities induced by cisplatin-the crucial limitation or potential therapeutic target? Int J Mol Sci. 2023;24(19). https:\/\/doi.org\/10.3390\/ijms241914574.","DOI":"10.3390\/ijms241914574"},{"issue":"8","key":"1198_CR37","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1007\/s11011-023-01290-8","volume":"38","author":"B Seyyedabadi","year":"2023","unstructured":"Seyyedabadi B, Babataheri S, Laher I, Soraya H. Neuroprotective effects of ivermectin against transient cerebral ischemia-reperfusion in rats. Metabolic Brain Disease 2023. 2023;38(8):2807\u201315. https:\/\/doi.org\/10.1007\/s11011-023-01290-8. 38.","journal-title":"Metabolic Brain Disease 2023"},{"issue":"2","key":"1198_CR38","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1080\/08923973.2023.2298895","volume":"46","author":"F Habibi Razi","year":"2024","unstructured":"Habibi Razi F, Mohammad Jafari R, Manavi MA, Sheibani M, Rashidian A, Tavangar SM, Beighmohammadi MT, Dehpour AR. Ivermectin ameliorates bleomycin-induced lung fibrosis in male rats by inhibiting the inflammation and oxidative stress. Immunopharmacol Immunotoxicol. 2024;46(2):183\u201391. https:\/\/doi.org\/10.1080\/08923973.2023.2298895.","journal-title":"Immunopharmacol Immunotoxicol"},{"issue":"12","key":"1198_CR39","doi-asserted-by":"publisher","first-page":"2977","DOI":"10.1016\/j.bbamcr.2016.09.012","volume":"1863","author":"M Redza-Dutordoir","year":"2016","unstructured":"Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim et Biophys Acta (BBA) - Mol Cell Res. 2016;1863(12):2977\u201392. https:\/\/doi.org\/10.1016\/j.bbamcr.2016.09.012.","journal-title":"Biochim et Biophys Acta (BBA) - Mol Cell Res"}],"container-title":["BMC Pharmacology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40360-026-01198-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-026-01198-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-026-01198-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:13:45Z","timestamp":1792584825000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40360-026-01198-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1198"],"URL":"https:\/\/doi.org\/10.1186\/s40360-026-01198-w","relation":{},"ISSN":["2050-6511"],"issn-type":[{"value":"2050-6511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"25 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors reviewed the manuscript and agreed to publish.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The manuscript leverages AI exclusively in the Introduction and Discussion, while we explicitly state the accepted limitations of AI-based assistance.","order":3,"name":"Ethics","label":"Disclosure","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"147"}}