2025/12/05 by Kathrin Weidele, Christian Werno, Steffi Treitschke +18 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Cancer Cells and Metastasis #Cancer Immunotherapy and Biomarkers #Melanoma and MAPK Pathways
paper · pdf · doi:10.1038/s44321-025-00339-8
openalex created_date 2025/12/05 · openalex publication_date 2025/12/05 · openalex updated_date 2026/08/01
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.