The Proteasome Inhibitor CEP-18770 Induces Cell Death in Medulloblastoma

Swastina Nath Varma, Shany Ye, Sara Ferlin, Charley Comer, Kian Cotton, Maria Niklison Chirou

Research output: Contribution to journalArticlepeer-review

Abstract

Medulloblastomas (MBs) represent the most prevalent malignant solid tumors in kids. The conventional treatment regimen for MBs includes surgical removal of the tumor, followed by radiation and chemotherapy. However, this approach is associated with significant morbidity and detrimental side effects. Consequently, there is a critical demand for more precise and less harmful treatments to enhance the quality of life for survivors. CEP-18770, a novel proteasome inhibitor that targets the 20S subunit, has emerged as a promising candidate, due to its anticancer activity in metastatic solid tumors and multiple myeloma, coupled with an acceptable safety profile. In this study, we aimed to assess the anticancer efficacy of CEP-18770 by employing a variety of MB patient-derived cells and cell lines. Our preclinical investigations revealed that CEP-18770 effectively inhibits proteasome activity and induces apoptosis in MBs cells. Furthermore, we discovered that CEP-18770 and cisplatin, a current component of MB therapy, exhibit a synergistic apoptotic effect. This paper shows that CEP-18770 holds potential as an adjunctive treatment for MB tumors, thereby paving the way for more targeted and less toxic therapeutic strategies.
Original languageEnglish
Article number672
JournalPharmaceutics
Volume16
Issue number5
Early online date16 May 2024
DOIs
Publication statusPublished - 31 May 2024

Data Availability Statement

Data is contained within the article and Supplementary Material.

Acknowledgements

The authors thank Stephen Ward from the University of Bath, for advice during the preparation of the manuscript.

Keywords

  • Medulloblastoma
  • brain tumors
  • proteasome inhibitors
  • CEP-18770
  • cancer

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