{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:23:27Z","timestamp":1787923407038,"version":"build-2784847793"},"reference-count":33,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020027","name":"Dr. Rolf M. Schwiete Stiftung","doi-asserted-by":"publisher","award":["2021-015"],"award-info":[{"award-number":["2021-015"]}],"id":[{"id":"10.13039\/501100020027","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2021-015"],"award-info":[{"award-number":["2021-015"]}],"id":[{"id":"https:\/\/ror.org\/03v7rwj71","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Cutaneous T-cell lymphomas (CTCL), most commonly mycosis fungoides and S\u00e9zary syndrome, are rare non-Hodgkin lymphomas. Advanced disease responds poorly to current treatments, highlighting the need for new molecularly targeted therapies. WEE1 is a central regulator of the G2\/M checkpoint and S-phase progression and has emerged as a therapeutic target in several malignancies, yet it has not been systematically explored in CTCL. Methods: We screened a library of more than 2200 kinase inhibitors in CTCL cell lines and selected adavosertib for further study. Its effects were tested in four CTCL lines; primary keratinocytes and fibroblasts; patient-derived malignant CD4+ T cells and healthy donor CD4+ T cells; and a MyLa xenograft model, using viability, apoptosis, cell-cycle, Western blot, and phospho-protein array assays. Results: Adavosertib reduced viability at submicromolar IC50 values (0.26\u20130.56 \u00b5M) across all four CTCL lines while largely sparing primary skin cells and was more active in malignant than in healthy donor CD4+ T cells. It induced apoptosis and cell-line-specific S-phase and\/or G2\/M accumulation, lowered WEE1 and phospho-CDK1 (Tyr15), and increased phospho-H2A.X. A phospho-protein array showed activation of checkpoint and stress signalling. In a preliminary xenograft experiment, adavosertib slowed MyLa tumour growth. Conclusions: These preclinical data identify WEE1 as a therapeutic target in CTCL and support further preclinical and early-phase clinical evaluation of adavosertib in this disease.<\/jats:p>","DOI":"10.3390\/cancers18172793","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:27:46Z","timestamp":1787920066000},"page":"2793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["WEE1 Inhibition as a Novel Therapeutic Strategy in Cutaneous T-Cell Lymphoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2667-6557","authenticated-orcid":false,"given":"Deniz","family":"\u00d6zistanbullu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Department of Dermatology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9911-1875","authenticated-orcid":false,"given":"Karola","family":"Bahrami","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Doll","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabi","family":"Reichenbach","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"P\u00f6schl","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-1917","authenticated-orcid":false,"given":"Raphael","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henner","family":"Stege","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Z\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Winkler","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology & Oncology Berlin-Buch GmbH, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St\u00e4dtisches Klinikum Karlsruhe, 76133 Karlsruhe, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan P.","family":"Nicolay","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, University of Heidelberg, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven R.","family":"Quist","sequence":"additional","affiliation":[{"name":"Clinic of Dermatology, Helix Medical Excellence Center Mainz, 55128 Mainz, Germany"},{"name":"Department of Dermatology, Otto-Von-Guericke Universit\u00e4t Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Meissner","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Schilling","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kleemann","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jindrich","family":"Cinatl","sequence":"additional","affiliation":[{"name":"Interdisciplinary Laboratory for Pediatric Tumor and Virus Research, Dr. Petra Joh Research Institute, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kippenberger","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41572-021-00296-9","article-title":"Cutaneous T cell lymphoma","volume":"7","author":"Dummer","year":"2021","journal-title":"Nat. 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