Micrometastasis-derived models enable drug testing for early-stage, high-risk melanoma patients

Weidele, Kathrin and Werno, Christian and Treitschke, Steffi and Botteron, Catherine and Hoffmann, Martin and Scheitler, Sebastian and Wöhrl, Lukas and Czyz, Zbigniew and Feliciello, Giancarlo and Weber, Florian and Ravikumar Varadarajan, Adithi and Warfsmann, Jens and Materna-Reichelt, Silvia and Katzer, Marie and Schreieder, Laura and Mohammadi, Parvaneh and Hosseini, Hedayatollah and Honarnejad, Kamran and Haferkamp, Sebastian and Werner-Klein, Melanie and Klein, Christoph A. (2026) Micrometastasis-derived models enable drug testing for early-stage, high-risk melanoma patients. EMBO MOLECULAR MEDICINE, 18 (1). pp. 297-324. ISSN 1757-4676, 1757-4684

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Abstract

Relapse in melanoma after targeted or immune therapy necessitates the rapid identification of effective alternatives. To address this gap, we investigated whether the timely generation of preclinical models for functional drug testing could reveal additional therapeutic options. Our study focused on: (i) the feasibility of generating in vivo and in vitro models from melanoma lymph node (LN)-derived disseminated cancer cells (DCCs) before relapse, (ii) the implementation of preclinical models to identify therapeutic alternatives, and (iii) the ability to detect patients who could benefit from early functional in vitro drug testing. Successful model generation was significantly associated with DCC quantity, LN origin, and mortality risk. All patient-derived xenograft models were available before patient death and, in 82% of cases, before relapse. Proof-of-concept in vitro drug screening using 315 anti-cancer drugs identified additional candidates, and coculture of DCCs and LN cells revealed specific T-cell activation and responses to immunotherapy. Our data establish a process for selecting melanoma patients at high risk of progression, enabling the timely generation of patient-derived models to support functionally guided treatment decisions at relapse.

Item Type: Article
Uncontrolled Keywords: TUMOR; XENOGRAFTS; DISULFIRAM; Disseminated Cancer Cells; Drug Testing; Metastasis; Precision Oncology; Preclinical Models
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Dermatologie und Venerologie
Medicine > Lehrstuhl für Pathologie
Medicine > Lehrstuhl für experimentelle Medizin und Therapieverfahren
Depositing User: Dr. Gernot Deinzer
Date Deposited: 23 Sep 2026 08:31
Last Modified: 23 Sep 2026 08:31
URI: https://pred.uni-regensburg.de/id/eprint/66278

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