{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:54:02Z","timestamp":1789206842793,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T00:00:00Z","timestamp":1384387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,3,15]]},"abstract":"<jats:p>As the options for systemic treatment of malignant melanoma (MM) increase, the need to develop biomarkers to identify patients who might benefit from cytotoxic chemotherapy becomes more apparent. In preclinical models, oxaliplatin has activity in cisplatin\u2010resistant cells. In this study, we have shown that oxaliplatin forms interstrand crosslinks (ICLs) in cellular DNA and that loss of the heterodimeric structure\u2010specific endonuclease XPF\u2010ERCC1 causes hypersensitivity to oxaliplatin in mammalian cells. XPF deficiency resulted in late S\u2010phase arrest and persistence of double\u2010strand breaks following oxaliplatin treatment. In a panel of 12 MM cell lines, oxaliplatin sensitivity correlated with XPF and ERCC1 protein levels. The knockdown of ERCC1 and XPF protein levels by RNA interference increased sensitivity of cancer cells to oxaliplatin; overexpression of exogenous ERCC1 significantly decreased drug sensitivity. Following immunohistochemical optimization, XPF protein levels were quantified in MM tissue samples from 183 patients, showing variation in expression and no correlation with prognosis. In 57 patients with MM treated with cisplatin or carboplatin, XPF protein levels did not predict the likelihood of clinical response. We propose that oxaliplatin should not be discarded as a potential treatment for MM on the basis of the limited activity of cisplatin in unselected patients. Moreover, we show that XPF\u2010ERCC1 protein levels are a key determinant of the sensitivity of melanoma cells to oxaliplatin <jats:italic>in vitro<\/jats:italic>. Immunohistochemical detection of XPF appears suitable for development as a tissue biomarker for potentially selecting patients for oxaliplatin treatment in a prospective clinical trial.<\/jats:p>","DOI":"10.1002\/ijc.28454","type":"journal-article","created":{"date-parts":[[2013,8,26]],"date-time":"2013-08-26T06:19:03Z","timestamp":1377497943000},"page":"1495-1503","source":"Crossref","is-referenced-by-count":18,"title":["XPF protein levels determine sensitivity of malignant melanoma cells to oxaliplatin chemotherapy: Suitability as a biomarker for patient selection"],"prefix":"10.1002","volume":"134","author":[{"given":"Stephanie B.","family":"Hatch","sequence":"first","affiliation":[{"name":"Department of Oncology Oxford NIHR Biomedical Research Centre, Cancer Research UK\u2010Medical Research Council Gray Institute for Radiation Oncology &amp; Biology, University of Oxford Oxford, Oxfordshire OX3 7DQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lonnie P.","family":"Swift","sequence":"additional","affiliation":[{"name":"Department of Oncology, Weatherall Institute of Molecular Medicine University of Oxford, John Radcliffe Hospital Oxford OX3 9DS, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Caporali","sequence":"additional","affiliation":[{"name":"Istituto Dermopatico dell'Immacolata\u2010IRCCS Laboratory of Molecular Oncology, Via dei Monti di Creta 104 00167 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Oncology Oxford NIHR Biomedical Research Centre, Cancer Research UK\u2010Medical Research Council Gray Institute for Radiation Oncology &amp; Biology, University of Oxford Oxford, Oxfordshire OX3 7DQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esme J.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Oncology Oxford NIHR Biomedical Research Centre, Cancer Research UK\u2010Medical Research Council Gray Institute for Radiation Oncology &amp; Biology, University of Oxford Oxford, Oxfordshire OX3 7DQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"MacGregor","sequence":"additional","affiliation":[{"name":"Department of Oncology Oxford NIHR Biomedical Research Centre, Cancer Research UK\u2010Medical Research Council Gray Institute for Radiation Oncology &amp; Biology, University of Oxford Oxford, Oxfordshire OX3 7DQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"D'Atri","sequence":"additional","affiliation":[{"name":"Istituto Dermopatico dell'Immacolata\u2010IRCCS Laboratory of Molecular Oncology, Via dei Monti di Creta 104 00167 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Middleton","sequence":"additional","affiliation":[{"name":"Department of Oncology Oxford NIHR Biomedical Research Centre, Cancer Research UK\u2010Medical Research Council Gray Institute for Radiation Oncology &amp; Biology, University of Oxford Oxford, Oxfordshire OX3 7DQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"McHugh","sequence":"additional","affiliation":[{"name":"Department of Oncology, Weatherall Institute of Molecular Medicine University of Oxford, John Radcliffe Hospital Oxford OX3 9DS, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky A.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Oncology Oxford NIHR Biomedical Research Centre, Cancer Research UK\u2010Medical Research Council Gray Institute for Radiation Oncology &amp; Biology, University of Oxford Oxford, Oxfordshire OX3 7DQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,14]]},"reference":[{"key":"e_1_2_5_2_1","unstructured":"Cancer Research UK. 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