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A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma
- Source :
- Cell Reports, Vol 32, Iss 2, Pp 107897-(2020)
- Publication Year :
- 2020
- Publisher :
- Uppsala universitet, Neuroonkologi, 2020.
-
Abstract
- Glioblastoma (GBM) is a malignant brain tumor with few therapeutic options. The disease presents with a complex spectrum of genomic aberrations, but the pharmacological consequences of these aberrations are partly unknown. Here, we report an integrated pharmacogenomic analysis of 100 patient-derived GBM cell cultures from the human glioma cell culture (HGCC) cohort. Exploring 1,544 drugs, we find that GBM has two main pharmacological subgroups, marked by differential response to proteasome inhibitors and mutually exclusive aberrations in TP53 and CDKN2A/B. We confirm this trend in cell and in xenotransplantation models, and identify both Bcl-2 family inhibitors and p53 activators as potentiators of proteasome inhibitors in GBM cells, We can further predict the responses of individual cell cultures to several existing drug classes, presenting opportunities for drug repurposing and design of stratified trials. Our functionally profiled biobank provides a valuable resource for the discovery of new treatments for GBM. Patrik Johansson, Cecilia Krona and Soumi Kundu share first authorship
- Subjects :
- Cellbiologi
Cell- och molekylärbiologi
Antineoplastic Agents
combination therapy
Bortezomib
Genetic Heterogeneity
Tumor Cells, Cultured
Animals
Humans
Gene Regulatory Networks
Molecular Targeted Therapy
Precision Medicine
data integration
lcsh:QH301-705.5
Cyclin-Dependent Kinase Inhibitor p16
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p15
Mice, Inbred BALB C
Genome, Human
glioblastoma
p53 reactivators
Cell Biology
multi-omics
biobank
lcsh:Biology (General)
Mutation
Tumor Suppressor Protein p53
Proteasome Inhibitors
Cell and Molecular Biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Reports, Vol 32, Iss 2, Pp 107897-(2020)
- Accession number :
- edsair.pmid.dedup....224df7b0a96b217a92523ab1aef4f7ea