Melanoma Brain Metastases Patient-Derived Organoids: An In Vitro Platform for Drug Screening.

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 (

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

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