DRUG AND SINGLE-CELL GENE EXPRESSION INTEGRATION IDENTIFIES SENSITIVE AND RESISTANT GLIOBLASTOMA CELL POPULATIONS.
Publication Title
bioRxiv
Document Type
Article
Publication Date
5-15-2025
Keywords
california; sjci; pni
Abstract
Glioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. A significant issue hindering GBM therapeutic development is intratumor heterogeneity. GBM tumors contain neoplastic cells within a spectrum of different transcriptional states. Identifying effective therapeutics requires a platform that predicts the differential sensitivity and resistance of these states to various treatments. Here, we developed a novel framework, ISOSCELES (Inferred cell Sensitivity Operating on the integration of Single-Cell Expression and L1000 Expression Signatures), to quantify the cellular drug sensitivity and resistance landscape. Using single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors, we identified compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct GBM cell states. We validated the significance of these findings
Area of Special Interest
Cancer
Area of Special Interest
Neurosciences (Brain & Spine)
Specialty/Research Institute
Oncology
Specialty/Research Institute
Neurosciences
Specialty/Research Institute
Pharmacy
DOI
10.1101/2025.05.15.654044
