{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T04:45:54Z","timestamp":1775105154019,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Uniwersytet Medyczny w Lublinie","doi-asserted-by":"publisher","award":["DS 474"],"award-info":[{"award-number":["DS 474"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Melanoma ranks 17th among the most frequently diagnosed cancers, with an upward trend in incidence. Treatment of this cancer is based on surgical removal of the lesion, but when metastases or recurrence occur, immunotherapy or chemotherapy is used. Most of the drugs used are characterized by numerous side effects or drug resistance that appears after some time of use. Therefore, multi-drug therapy is more often considered. The aim of the study was to assess the nature of the pharmacodynamic interaction of five different cytostatics (in a fixed dose ratio of 1:1) using a mathematical-statistical method\u2014isobolographic analysis. The experiments were conducted on four human malignant melanoma cell lines (A375, SK-MEL28, FM55M2, FM55P) and studied all possible (ten) pairs of combinations of five standard cancer chemotherapy drugs (based on the MTT test): cisplatin, mitoxantrone, docetaxel, vemurafenib, and selumetinib. Our experiments showed that the most advantageous combination was the combination of vemurafenib with docetaxel for human melanoma lines\u2014statistically significant synergy interaction for three cell lines. Also noteworthy are the combinations: cisplatin with mitoxantrone, vemurafenib with selumetinib, and vemurafenib with mitoxantrone. From a therapeutic point of view, the worst combination is cisplatin with docetaxel and cisplatin with selumetinib (interaction with a tendency to antagonism for the two cell lines). Monotherapy for melanoma does not produce good results, so the best drug combinations are sought, which would improve long-term, durable patient response and overcome drug resistance. It would also be good if the combination used caused fewer side effects than monotherapy, and this could be achieved in the case of using synergistic combinations.<\/jats:p>","DOI":"10.1007\/s00210-025-04712-9","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T09:45:46Z","timestamp":1762940746000},"page":"5843-5854","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of pharmacodynamic interactions of two-drug combinations of five selected cytostatics in an in vitro model of human melanoma: an isobolographic analysis"],"prefix":"10.1007","volume":"399","author":[{"given":"Paula","family":"Wr\u00f3blewska-\u0141uczka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"G\u00f3ralczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarogniew J.","family":"\u0141uszczki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"issue":"1","key":"4712_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-018-1471-1","volume":"16","author":"IW Achkar","year":"2018","unstructured":"Achkar IW, Abdulrahman N, Al-Sulaiti H, Joseph JM, Uddin S, Mraiche F (2018) Cisplatin based therapy: the role of the mitogen activated protein kinase signaling pathway. J Transl Med 16(1):96. https:\/\/doi.org\/10.1186\/s12967-018-1471-1","journal-title":"J Transl Med"},{"issue":"1\u20133","key":"4712_CR2","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/s1011-1344(01)00198-1","volume":"63","author":"BK Armstrong","year":"2001","unstructured":"Armstrong BK, Kricker A (2001) The epidemiology of UV induced skin cancer. J Photochem Photobiol B 63(1\u20133):8\u201318. https:\/\/doi.org\/10.1016\/s1011-1344(01)00198-1","journal-title":"J Photochem Photobiol B"},{"issue":"3","key":"4712_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-015-0293-5","volume":"14","author":"M Atefi","year":"2015","unstructured":"Atefi M, Titz B, Avramis E, Ng C, Wong DJ, Lassen A, Cerniglia M, Escuin-Ordinas H, Foulad D, Comin-Anduix B, Graeber TG, Ribas A (2015) Combination of pan-RAF and MEK inhibitors in NRAS mutant melanoma. Mol Cancer 14(3):27. https:\/\/doi.org\/10.1186\/s12943-015-0293-5","journal-title":"Mol Cancer"},{"key":"4712_CR4","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0031-6997(25)00026-2","volume":"41","author":"MC Berenbaum","year":"1989","unstructured":"Berenbaum MC (1989) What is synergy? Pharmacol Rev 41:93\u2013141","journal-title":"Pharmacol Rev"},{"issue":"9","key":"4712_CR5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093233","volume":"21","author":"K Bukowski","year":"2020","unstructured":"Bukowski K, Kciuk M, Kontek R (2020) Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci 21(9):3233. https:\/\/doi.org\/10.3390\/ijms21093233","journal-title":"Int J Mol Sci"},{"issue":"4","key":"4712_CR6","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1097\/RCT.0000000000001315","volume":"46","author":"M Chen","year":"2022","unstructured":"Chen M, Smith DA, Yoon JG, Vos D, Kikano EG, Tirumani SH, Ramaiya NH (2022) A decade of success in melanoma immunotherapy and targeted therapy: what every radiologist should know. J Comput Assist Tomogr 46(4):621\u2013632. https:\/\/doi.org\/10.1097\/RCT.0000000000001315","journal-title":"J Comput Assist Tomogr"},{"issue":"11","key":"4712_CR7","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1080\/10428190802353591","volume":"49","author":"TC Chou","year":"2008","unstructured":"Chou TC (2008) Preclinical versus clinical drug combination studies. Leuk Lymphoma 49(11):2059\u20132080. https:\/\/doi.org\/10.1080\/10428190802353591","journal-title":"Leuk Lymphoma"},{"issue":"5","key":"4712_CR8","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1177\/2472555220970917","volume":"26","author":"DA Close","year":"2021","unstructured":"Close DA, Kirkwood JM, Fecek RJ, Storkus WJ, Johnston PA (2021) Unbiased high-throughput drug combination pilot screening identifies synergistic drug combinations effective against patient-derived and drug-resistant melanoma cell lines. SLAS Discov 26(5):712\u2013729. https:\/\/doi.org\/10.1177\/2472555220970917","journal-title":"SLAS Discov"},{"issue":"4 Suppl","key":"4712_CR9","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1188\/17.CJON.S4.11-29","volume":"21","author":"M Czupryn","year":"2017","unstructured":"Czupryn M, Cisneros J (2017) BRAF\/MEK inhibitor therapy: consensus statement from the faculty of the melanoma nursing initiative on managing adverse events and potential drug interactions. Clin J Oncol Nurs 21(4 Suppl):11\u201329. https:\/\/doi.org\/10.1188\/17.CJON.S4.11-29","journal-title":"Clin J Oncol Nurs"},{"issue":"1","key":"4712_CR10","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1080\/13543784.2022.2027366","volume":"31","author":"DK DePalo","year":"2022","unstructured":"DePalo DK, Tarhini A, Zager JS (2022) The treatment of advanced melanoma: a review of systemic and local therapies in combination with immune checkpoint inhibitors in phase 1 and 2 clinical trials. Expert Opin Investig Drugs 31(1):95\u2013104. https:\/\/doi.org\/10.1080\/13543784.2022.2027366","journal-title":"Expert Opin Investig Drugs"},{"issue":"8","key":"4712_CR11","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1038\/s41416-022-01903-6","volume":"127","author":"MK Doherty","year":"2022","unstructured":"Doherty MK, Tam VC, McNamara MG, Jang R, Hedley D, Chen E, Dhani N, Tang P, Sim HW, O\u2019Kane GM, DeLuca S, Wang L, Pedutem T, Knox JJ (2022) Randomised, phase II study of selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer. Br J Cancer 127(8):1473\u20131478. https:\/\/doi.org\/10.1038\/s41416-022-01903-6","journal-title":"Br J Cancer"},{"key":"4712_CR12","doi-asserted-by":"publisher","unstructured":"Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, Hamid O, Schuchter L, Cebon J, Ibrahim N, Kudchadkar R, Burris HA 3rd, Falchook G, Algazi A, Lewis K, Long GV, Puzanov I, Lebowitz P, Singh A, Little S, Sun P, Allred A, Ouellet D, Kim KB, Patel K, Weber J (2012) Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 1(18):1694\u20131703. https:\/\/doi.org\/10.1056\/NEJMoa1210093","DOI":"10.1056\/NEJMoa1210093"},{"key":"4712_CR13","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/978-3-319-91442-8_6","volume":"211","author":"C Garbe","year":"2018","unstructured":"Garbe C, Eigentler TK (2018) Vemurafenib. Recent Results Cancer Res 211:77\u201389. https:\/\/doi.org\/10.1007\/978-3-319-91442-8_6","journal-title":"Recent Results Cancer Res"},{"issue":"1","key":"4712_CR14","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1634\/theoncologist.2010-0190","volume":"16","author":"C Garbe","year":"2011","unstructured":"Garbe C, Eigentler TK, Keilholz U, Hauschild A, Kirkwood JM (2011) Systematic review of medical treatment in melanoma: current status and future prospects. Oncologist 16(1):5\u201324. https:\/\/doi.org\/10.1634\/theoncologist.2010-0190","journal-title":"Oncologist"},{"issue":"1","key":"4712_CR15","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/1047-2797(93)90017-x","volume":"3","author":"CF Garland","year":"1993","unstructured":"Garland CF, Garland FC, Gorham ED (1993) Rising trends in melanoma. An hypothesis concerning sunscreen effectiveness. Ann Epidemiol 3(1):103\u2013110. https:\/\/doi.org\/10.1016\/1047-2797(93)90017-x","journal-title":"Ann Epidemiol"},{"issue":"6","key":"4712_CR16","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022608","volume":"10","author":"HV Goodson","year":"2018","unstructured":"Goodson HV, Jonasson EM (2018) Microtubules and microtubule-associated proteins. Cold Spring Harb Perspect Biol 10(6):a022608. https:\/\/doi.org\/10.1101\/cshperspect.a022608","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"1","key":"4712_CR17","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1006\/gyno.1998.5317","volume":"73","author":"A Husain","year":"1999","unstructured":"Husain A, Sabbatini P, Spriggs D, Fennelly D, Aghajanian C, Barakat R, Curtin J, Venkatraman E, Hoskins W, Markman M (1999) Phase II trial of intraperitoneal cisplatin and mitoxantrone in patients with persistent ovarian cancer. Gynecol Oncol 73(1):96\u2013101. https:\/\/doi.org\/10.1006\/gyno.1998.5317","journal-title":"Gynecol Oncol"},{"issue":"5","key":"4712_CR18","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.bcp.2010.04.029","volume":"1","author":"GS Inamdar","year":"2010","unstructured":"Inamdar GS, Madhunapantula SV, Robertson GP (2010) Targeting the MAPK pathway in melanoma: why some approaches succeed and other fail. Biochem Pharmacol 1(5):624\u2013637. https:\/\/doi.org\/10.1016\/j.bcp.2010.04.029","journal-title":"Biochem Pharmacol"},{"key":"4712_CR19","doi-asserted-by":"publisher","unstructured":"Jamal R, Lapointe R, Cocolakis E, Th\u00e9bault P, Kazemi S, Friedmann JE, Dionne J, Cailhier JF, B\u00e9langer K, Ayoub JP, Le H, Lambert C, El-Hajjar J, van Kempen LC, Spatz A, Miller WH Jr. (2017) Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin\/paclitaxel in unresectable stage III or stage IV melanoma. J Immunother Cancer 5(1):83. https:\/\/doi.org\/10.1186\/s40425-017-0290-x","DOI":"10.1186\/s40425-017-0290-x"},{"issue":"11","key":"4712_CR20","first-page":"6473","volume":"34","author":"A Jarz\u0105b","year":"2014","unstructured":"Jarz\u0105b A, Grabarska A, Kie\u0142bus M, Jeleniewicz W, Dmoszy\u0144ska-Graniczka M, Skalicka-Wo\u017aniak K, Sieniawska E, Polberg K, Stepulak A (2014) Osthole induces apoptosis, suppresses cell-cycle progression and proliferation of cancer cells. Anticancer Res 34(11):6473\u20136480","journal-title":"Anticancer Res"},{"issue":"1","key":"4712_CR21","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/coa.13876","volume":"47","author":"T Kumai","year":"2022","unstructured":"Kumai T, Komatsuda H, Wakisaka R, Yamaki H, Kono M, Hayashi R, Kishibe K, Takahara M, Katada A, Hayashi T, Harabuchi Y (2022) Concurrent chemoradiotherapy with cisplatin and docetaxel for head and neck squamous cell carcinoma. Clin Otolaryngol 47(1):228\u2013233. https:\/\/doi.org\/10.1111\/coa.13876","journal-title":"Clin Otolaryngol"},{"issue":"13","key":"4712_CR22","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1056\/NEJMoa1408868","volume":"371","author":"J Larkin","year":"2014","unstructured":"Larkin J, Ascierto PA, Dr\u00e9no B, Atkinson V, Liszkay G, Maio M, Mandal\u00e0 M, Demidov L, Stroyakovskiy D, Thomas L, de la Cruz-Merino L, Dutriaux C, Garbe C, Sovak MA, Chang I, Choong N, Hack SP, McArthur GA, Ribas A (2014) Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 371(13):1867\u20131876. https:\/\/doi.org\/10.1056\/NEJMoa1408868","journal-title":"N Engl J Med"},{"key":"4712_CR23","doi-asserted-by":"crossref","unstructured":"Legut M, Lipka D, Filipczak N, Piwoni A, Kozubek A, Gubernator J (2014) Anacardic acid enhances the anticancer activity of liposomal mitoxantrone towards melanoma cell lines - in vitro studies. Int J Nanomedicine 23(9):653\u2013668. 10.2147\/IJN.S54911 . Erratum.In:IntJNanomedicine.2015Sep,14(10),pp.5769. 10.2147\/IJN.S83181","DOI":"10.2147\/IJN.S54911"},{"issue":"6","key":"4712_CR24","first-page":"1257","volume":"7","author":"H Lenk","year":"1987","unstructured":"Lenk H, M\u00fcller U, Tanneberger S (1987) Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. Anticancer Res 7(6):1257\u20131264","journal-title":"Anticancer Res"},{"issue":"2","key":"4712_CR25","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S0022-3565(25)03549-9","volume":"96","author":"JT Litchfield Jr","year":"1949","unstructured":"Litchfield JT Jr, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96(2):99\u2013113","journal-title":"J Pharmacol Exp Ther"},{"issue":"20","key":"4712_CR26","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1056\/NEJMoa1406037","volume":"371","author":"GV Long","year":"2014","unstructured":"Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, Chiarion Sileni V, Lebbe C, Mandal\u00e0 M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Casey M, Ouellet D, Martin AM, Le N, Patel K, Flaherty K (2014) Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 371(20):1877\u20131888. https:\/\/doi.org\/10.1056\/NEJMoa1406037","journal-title":"N Engl J Med"},{"issue":"18","key":"4712_CR27","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.1517\/14656566.2013.849244","volume":"14","author":"JJ Luke","year":"2013","unstructured":"Luke JJ, Ott PA (2013) Kinase inhibitors and immune check-point blockade for the treatment of metastatic melanoma and advanced cancer: synergistic or antagonistic? Expert Opin Pharmacother 14(18):2457\u20132462. https:\/\/doi.org\/10.1517\/14656566.2013.849244","journal-title":"Expert Opin Pharmacother"},{"key":"4712_CR28","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s00210-007-0144-z","volume":"375","author":"JJ Luszczki","year":"2007","unstructured":"Luszczki JJ (2007) Isobolographic analysis of interaction between drugs with nonparallel dose-response relationship curves: a practical application. Naunyn Schmiedebergs Arch Pharmacol 375:105\u2013114","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"2","key":"4712_CR29","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1055\/s-0040-1709126","volume":"36","author":"VT Ma","year":"2020","unstructured":"Ma VT, Haring CT, Warrier G, Swiecicki PL (2020) Targeted therapy and traditional chemotherapy in melanoma and cutaneous squamous cell carcinoma. Facial Plast Surg 36(2):186\u2013193. https:\/\/doi.org\/10.1055\/s-0040-1709126","journal-title":"Facial Plast Surg"},{"issue":"12","key":"4712_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126752","volume":"23","author":"P Marz\u0119da","year":"2022","unstructured":"Marz\u0119da P, Wr\u00f3blewska-\u0141uczka P, Drozd M, Florek-\u0141uszczki M, Za\u0142uska-Ogryzek K, \u0141uszczki JJ (2022) Cannabidiol interacts antagonistically with cisplatin and additively with mitoxantrone in various melanoma cell lines-an isobolographic analysis. Int J Mol Sci 23(12):6752. https:\/\/doi.org\/10.3390\/ijms23126752","journal-title":"Int J Mol Sci"},{"issue":"11","key":"4712_CR31","doi-asserted-by":"publisher","first-page":"5941","DOI":"10.21873\/anticanres.12041","volume":"37","author":"A Najem","year":"2017","unstructured":"Najem A, Krayem M, Perdrix A, Kerger J, Awada A, Journe F, Ghanem G (2017) New drug combination strategies in melanoma: current status and future directions. Anticancer Res 37(11):5941\u20135953. https:\/\/doi.org\/10.21873\/anticanres.12041","journal-title":"Anticancer Res"},{"issue":"23","key":"4712_CR32","doi-asserted-by":"publisher","first-page":"7848","DOI":"10.1039\/c8dt90088d","volume":"47","author":"R Oun","year":"2018","unstructured":"Oun R, Moussa YE, Wheate NJ (2018) The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans 47(23):7848. https:\/\/doi.org\/10.1039\/c8dt90088d","journal-title":"Dalton Trans"},{"issue":"12","key":"4712_CR33","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-016-0436-y","volume":"17","author":"M Polkowska","year":"2016","unstructured":"Polkowska M, Czepielewska E, Koz\u0142owska-Wojciechowska M (2016) Drug combinations as the new standard for melanoma treatment. Curr Treat Options Oncol 17(12):61. https:\/\/doi.org\/10.1007\/s11864-016-0436-y","journal-title":"Curr Treat Options Oncol"},{"issue":"10","key":"4712_CR34","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/sj.bjc.6604891","volume":"100","author":"KS Smalley","year":"2009","unstructured":"Smalley KS, Flaherty KT (2009) Integrating BRAF\/MEK inhibitors into combination therapy for melanoma. Br J Cancer 100(10):431\u2013435. https:\/\/doi.org\/10.1038\/sj.bjc.6604891","journal-title":"Br J Cancer"},{"issue":"9","key":"4712_CR35","doi-asserted-by":"publisher","first-page":"3005","DOI":"10.1016\/j.biomaterials.2013.12.018","volume":"35","author":"W Song","year":"2014","unstructured":"Song W, Tang Z, Zhang D, Zhang Y, Yu H, Li M, Lv S, Sun H, Deng M, Chen X (2014) Anti-tumor efficacy of c(RGDfK)-decorated polypeptide-based micelles co-loaded with docetaxel and cisplatin. Biomaterials 35(9):3005\u20133014. https:\/\/doi.org\/10.1016\/j.biomaterials.2013.12.018","journal-title":"Biomaterials"},{"issue":"3","key":"4712_CR36","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209\u2013249. https:\/\/doi.org\/10.3322\/caac.21660","journal-title":"CA Cancer J Clin"},{"issue":"11","key":"4712_CR37","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1177\/1947601912440575","volume":"2","author":"RJ Tallarida","year":"2011","unstructured":"Tallarida RJ (2011) Quantitative methods for assessing drug synergism. Genes Cancer 2(11):1003\u20131008. https:\/\/doi.org\/10.1177\/1947601912440575","journal-title":"Genes Cancer"},{"issue":"11","key":"4712_CR38","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/0024-3205(89)90148-3","volume":"45","author":"RJ Tallarida","year":"1989","unstructured":"Tallarida RJ, Porreca F, Cowan A (1989) Statistical analysis of drug-drug and site-site interactions with isobolograms. Life Sci 45(11):947\u2013961. https:\/\/doi.org\/10.1016\/0024-3205(89)90148-3","journal-title":"Life Sci"},{"issue":"3","key":"4712_CR39","first-page":"265","volume":"19","author":"E Topuz","year":"1998","unstructured":"Topuz E, Saip P, Aydmer A, Saliho\u011flu Y, Berkman S, Bengisu E (1998) Intraperitoneal cisplatin-mitoxantrone and intravenous ifosfamide combination as first-line treatment of ovarian cancer. Eur J Gynaecol Oncol 19(3):265\u2013270","journal-title":"Eur J Gynaecol Oncol"},{"issue":"15","key":"4712_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20153663","volume":"20","author":"A Wawruszak","year":"2019","unstructured":"Wawruszak A, Luszczki JJ, Kalafut J, Okla K, Halasa M, Rivero-Muller A, Stepulak A (2019) Additive pharmacological interaction between cisplatin (CDDP) and histone deacetylase inhibitors (HDIs) in MDA-MB-231 triple negative breast cancer (TNBC) cells with altered notch1 activity-an isobolographic analysis. Int J Mol Sci 20(15):3663. https:\/\/doi.org\/10.3390\/ijms20153663","journal-title":"Int J Mol Sci"},{"issue":"2","key":"4712_CR41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020537","volume":"22","author":"P Wr\u00f3blewska-\u0141uczka","year":"2021","unstructured":"Wr\u00f3blewska-\u0141uczka P, Grabarska A, Florek-\u0141uszczki M, Plewa Z, \u0141uszczki JJ (2021) Synergy, additivity, and antagonism between cisplatin and selected coumarins in human melanoma cells. Int J Mol Sci 22(2):537. https:\/\/doi.org\/10.3390\/ijms22020537","journal-title":"Int J Mol Sci"},{"issue":"17","key":"4712_CR42","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23179641","volume":"23","author":"P Wr\u00f3blewska-\u0141uczka","year":"2022","unstructured":"Wr\u00f3blewska-\u0141uczka P, Cabaj J, B\u0105k W, Bargie\u0142 J, Grabarska A, G\u00f3ralczyk A, \u0141uszczki JJ (2022a) Additive interactions between betulinic acid and two taxanes in in vitro tests against four human malignant melanoma cell lines. Int J Mol Sci 23(17):9641. https:\/\/doi.org\/10.3390\/ijms23179641","journal-title":"Int J Mol Sci"},{"issue":"1","key":"4712_CR43","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010212","volume":"24","author":"P Wr\u00f3blewska-\u0141uczka","year":"2022","unstructured":"Wr\u00f3blewska-\u0141uczka P, Grabarska A, G\u00f3ralczyk A, Marz\u0119da P, \u0141uszczki JJ (2022b) Fraxetin interacts additively with cisplatin and mitoxantrone, antagonistically with docetaxel in various human melanoma cell lines-an isobolographic analysis. Int J Mol Sci 24(1):212. https:\/\/doi.org\/10.3390\/ijms24010212","journal-title":"Int J Mol Sci"},{"issue":"9","key":"4712_CR44","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28093889","volume":"28","author":"P Wr\u00f3blewska-\u0141uczka","year":"2023","unstructured":"Wr\u00f3blewska-\u0141uczka P, G\u00f3ralczyk A, \u0141uszczki JJ (2023) Synergy, additivity and antagonism between esculetin and six commonly used chemotherapeutics in various malignant melanoma cell lines-an isobolographic analysis. Molecules 28(9):3889. https:\/\/doi.org\/10.3390\/molecules28093889","journal-title":"Molecules"},{"issue":"23","key":"4712_CR45","doi-asserted-by":"publisher","first-page":"3268","DOI":"10.1080\/15384101.2016.1242537","volume":"15","author":"S Yasuhira","year":"2016","unstructured":"Yasuhira S, Shibazaki M, Nishiya M, Maesawa C (2016) Paclitaxel-induced aberrant mitosis and mitotic slippage efficiently lead to proliferative death irrespective of canonical apoptosis and p53. Cell Cycle 15(23):3268\u20133277. https:\/\/doi.org\/10.1080\/15384101.2016.1242537","journal-title":"Cell Cycle"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04712-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-025-04712-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-04712-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T03:19:57Z","timestamp":1775099997000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-025-04712-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["4712"],"URL":"https:\/\/doi.org\/10.1007\/s00210-025-04712-9","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"assertion":[{"value":"27 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Institutional review board statement"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}