Subgroup-Enriched Pathways and Kinase Signatures in Medulloblastoma Patient-Derived Xenografts
Kristin L Leskoske1, Krystine Garcia-Mansfield1,2, Ritin Sharma1,2
1Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, United States.
Journal of Proteome Research
|August 17, 2022
Summary
This study identified new therapeutic targets for medulloblastoma (MB), a common pediatric brain tumor. Proteomic analysis of MB models revealed MYC activity in Group 3 MB, suggesting potential treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Medulloblastoma (MB) is the most common malignant pediatric brain tumor.
- MB comprises four main molecular subgroups (WNT, SHH, G3, G4), with Group 3 MB having a poor prognosis.
- Therapeutic development for MB, particularly G3, is challenged by subgroup heterogeneity and limited actionable mutations.
Purpose of the Study:
- To identify novel therapeutic targets for medulloblastoma (MB).
- To characterize the proteomic and phosphoproteomic profiles of MB subgroups.
- To evaluate the utility of patient-derived xenograft (PDX) models for MB research.
Main Methods:
- Deep expression proteomics and phosphoproteomics were performed on 20 MB PDX models.
- PDX models represented SHH, G3, and G4 molecular subgroups.
- Proteomic data were analyzed to identify signaling pathways and potential therapeutic targets.
Main Results:
- Proteomic profiles of MB PDX models closely mirrored primary human MB tumors.
- SHH PDX models showed enrichment in NFκB and p38 MAPK signaling pathways.
- G3 PDX models exhibited significant MYC activity, correlating with actinomycin D sensitivity.
Conclusions:
- The study identified candidate pathways for novel MB therapies.
- MYC signaling is a potential therapeutic target for Group 3 medulloblastoma.
- PDX models are valuable tools for understanding MB biology and developing targeted treatments.
