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Updated: Jan 9, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Micrometastasis-derived models enable drug testing for early-stage, high-risk melanoma patients
Kathrin Weidele1, Christian Werno1, Steffi Treitschke1
1Fraunhofer-Institute for Toxicology and Experimental Medicine, Division of Personalized Tumor Therapy, Am Biopark 9, Regensburg, 93053, Germany.
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.
Insights
Generating patient-derived melanoma models before relapse can identify new therapies. This approach supports personalized treatment decisions for patients at high risk of disease progression.
Area of Science:
- Oncology
- Translational Medicine
- Cancer Research
Background:
- Melanoma relapse after targeted or immune therapy requires identification of alternative treatments.
- Preclinical models are crucial for functional drug testing to discover novel therapeutic options.
Purpose of the Study:
- To assess the feasibility of generating in vivo and in vitro models from melanoma lymph node (LN)-derived disseminated cancer cells (DCCs) before relapse.
- To implement these preclinical models for identifying alternative therapeutic strategies.
- To determine if early functional in vitro drug testing can identify patients who would benefit.
Main Methods:
- Generation of patient-derived xenograft (PDX) models and in vitro cultures from melanoma LN-derived DCCs.
- In vitro drug screening of 315 anti-cancer drugs using established models.
- Coculture assays of DCCs and LN cells to assess immune responses.
Main Results:
- Successful model generation correlated with DCC quantity, LN origin, and mortality risk.
- PDX models were available before patient death in all cases and before relapse in 82%.
- Drug screening identified additional therapeutic candidates, and coculture revealed T-cell activation and immunotherapy responses.
Conclusions:
- A process for selecting high-risk melanoma patients for timely model generation was established.
- Patient-derived models facilitate functionally guided treatment decisions at melanoma relapse.
- This strategy supports the discovery of alternative therapies for refractory melanoma.
