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Updated: Jun 14, 2025
Author Spotlight: Recreating Melanoma Complexity with Patient-Derived Organoids for Immunotherapy Evaluation
Published on: September 6, 2024
Melanoma Brain Metastases Patient-Derived Organoids: An In Vitro Platform for Drug Screening
Saif-Eldin Abedellatif1, Racha Hosni1, Andreas Waha2
1Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany.
Background And Aims:
Brain metastases are prevalent in the late stages of malignant melanoma. Multimodal therapy remains challenging. Patient-derived organoids (PDOs) represent a valuable pre-clinical model, faithfully recapitulating key aspects of the original tumor, including the heterogeneity and the mutational status. This study aimed to establish PDOs from melanoma brain metastases (MBM-PDOs) and to test the feasibility of using them as a model for in vitro targeted-therapy drug testing.
Methods:
Surgical resection samples from eight patients with melanoma brain metastases were used to establish MBM-PDOs. The samples were enzymatically dissociated followed by seeding into low-attachment plates to generate floating organoids. The MBM-PDOs were characterized genetically, histologically, and immunohistologically and compared with the parental tissue. The MBM-PDO cultures were exposed to dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) followed by a cell viability assessment.
Results:
Seven out of eight cases were successfully cultivated, maintaining the histological, immunohistological phenotype, and the mutational status of the parental tumors. Five out of seven cases harbored BRAF V600E mutations and were responsive to BRAF and MEK inhibitors in vitro. Two out of seven cases were BRAF wild type: one case harboring an NRAS mutation and the other harboring a KIT mutation, and both were resistant to BRAF and MEK inhibitor therapy.
Conclusions:
We successfully established PDOs from melanoma brain metastases surgical specimens, which exhibited a consistent histological and mutational profile with the parental tissue. Using FDA-approved BRAF and MEK inhibitors, our data demonstrate the feasibility of employing MBM-PDOs for targeted-therapy in vitro testing.
Insights
Patient-derived organoids from melanoma brain metastases were successfully established. These models accurately reflect tumor genetics and show potential for in vitro testing of targeted therapies like BRAF and MEK inhibitors.
Area of Science:
- Oncology
- Cancer Research
- Translational Medicine
Background:
- Brain metastases are common in advanced melanoma, posing therapeutic challenges.
- Patient-derived organoids (PDOs) offer a preclinical model that preserves tumor heterogeneity and mutational status.
- Melanoma brain metastases (MBM) require effective therapeutic strategies.
Purpose of the Study:
- To establish and characterize PDOs from melanoma brain metastases (MBM-PDOs).
- To evaluate the feasibility of using MBM-PDOs for in vitro drug testing of targeted therapies.
- To assess the response of MBM-PDOs to BRAF and MEK inhibitors.
Main Methods:
- Surgical samples from eight melanoma brain metastasis patients were used.
- Melanoma brain metastasis patient-derived organoids (MBM-PDOs) were generated via enzymatic dissociation and low-attachment culture.
- MBM-PDOs underwent genetic, histological, and immunohistological characterization.
- MBM-PDOs were treated with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), followed by cell viability assessment.
Main Results:
- Seven of eight MBM-PDO cultures were successfully established, maintaining parental tumor characteristics.
- Five MBM-PDOs with BRAF V600E mutations responded to BRAF and MEK inhibitors in vitro.
- Two BRAF wild-type MBM-PDOs (one NRAS-mutated, one KIT-mutated) were resistant to these inhibitors.
Conclusions:
- Successfully established MBM-PDOs that retain histological and mutational fidelity to the original tumors.
- Demonstrated the utility of MBM-PDOs for in vitro drug screening of targeted therapies.
- MBM-PDOs provide a viable platform for personalized medicine approaches in melanoma brain metastases.
