Melanoma Brain Metastases Patient-Derived Organoids: an in Vitro Platform for Drug Screening

Saif-Eldin Abedellatif; Racha Hosni; Andreas Waha; Gerrit H. Gielen; Mohammed Banat; Motaz Hamed; Erdem Güresir; Anne Fröhlich; Judith Sirokay; Anna-Lena Wulf; Glen Kristiansen; Torsten Pietsch; Hartmut Vatter; Michael Hölzel; Matthias Schneider; Marieta Ioana Toma

doi:10.20944/preprints202407.0598.v1

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preprints.org > medicine and pharmacology > oncology and oncogenics > doi: 10.20944/preprints202407.0598.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Melanoma Brain Metastases Patient-Derived Organoids: an in Vitro Platform for Drug Screening

Saif-Eldin Abedellatif

^* ,

Version 1 : Received: 6 July 2024 / Approved: 6 July 2024 / Online: 8 July 2024 (09:04:23 CEST)

How to cite: Abedellatif, S.-E.; Hosni, R.; Waha, A.; Gielen, G. H.; Banat, M.; Hamed, M.; Güresir, E.; Fröhlich, A.; Sirokay, J.; Wulf, A.-L.; Kristiansen, G.; Pietsch, T.; Vatter, H.; Hölzel, M.; Schneider, M.; Toma, M. I. Melanoma Brain Metastases Patient-Derived Organoids: an in Vitro Platform for Drug Screening. Preprints 2024, 2024070598. https://doi.org/10.20944/preprints202407.0598.v1 Abedellatif, S.-E.; Hosni, R.; Waha, A.; Gielen, G. H.; Banat, M.; Hamed, M.; Güresir, E.; Fröhlich, A.; Sirokay, J.; Wulf, A.-L.; Kristiansen, G.; Pietsch, T.; Vatter, H.; Hölzel, M.; Schneider, M.; Toma, M. I. Melanoma Brain Metastases Patient-Derived Organoids: an in Vitro Platform for Drug Screening. Preprints 2024, 2024070598. https://doi.org/10.20944/preprints202407.0598.v1

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MDPI and ACS Style

Abedellatif, S.-E.; Hosni, R.; Waha, A.; Gielen, G. H.; Banat, M.; Hamed, M.; Güresir, E.; Fröhlich, A.; Sirokay, J.; Wulf, A.-L.; Kristiansen, G.; Pietsch, T.; Vatter, H.; Hölzel, M.; Schneider, M.; Toma, M. I. Melanoma Brain Metastases Patient-Derived Organoids: an in Vitro Platform for Drug Screening. Preprints 2024, 2024070598. https://doi.org/10.20944/preprints202407.0598.v1

APA Style

Abedellatif, S. E., Hosni, R., Waha, A., Gielen, G. H., Banat, M., Hamed, M., Güresir, E., Fröhlich, A., Sirokay, J., Wulf, A. L., Kristiansen, G., Pietsch, T., Vatter, H., Hölzel, M., Schneider, M., & Toma, M. I. (2024). Melanoma Brain Metastases Patient-Derived Organoids: an <em>in Vitro</em> Platform for Drug Screening. Preprints. https://doi.org/10.20944/preprints202407.0598.v1

Chicago/Turabian Style

Abedellatif, S., Matthias Schneider and Marieta Ioana Toma. 2024 "Melanoma Brain Metastases Patient-Derived Organoids: an <em>in Vitro</em> Platform for Drug Screening" Preprints. https://doi.org/10.20944/preprints202407.0598.v1

Abstract

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. Samples were enzymatically dissociated followed by seeding into low-attachment plates to generate floating organoids. The MBM-PDOs were characterized genetically, histologically, immunohistologically and compared with the parental tissue. The MBM-PDO cultures were exposed to dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) followed by cell viability assessment.Results: Seven out of eight cases were successfully cultivated, maintaining the histological, immunhistological 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. Conclusion: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 demonstrates the feasibility of employing MBM-PDOs for targeted-therapy in vitro testing.

Keywords

Melanoma; brain metastases; BRAF; Organoids

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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