English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Glioblastoma (GBM) remains a highly malignant and incurable brain tumour. The inability to achieve clinical improvements in GBM treatment can be attributed to the excessive heterogeneity and plasticity of GBM cells, which is reflected by the presence of various cellular states within each tumour. How each of these tumour cell subtypes respond to therapy remains largely unknown. In this work, we developed a functional diagnostic analysis pipeline to measure therapeutic activity in GBM tumour cells at single-cell resolution using mass cytometry by time-of-flight (CyTOF). By applying an optimised GBM-specific and therapy-tailored antibody panel, we measured therapeutic activity upon exposure to ionising radiation (RT) or a small molecule MDM2 inhibitor (AMG232) in a cohort of patient-derived GBM cell lines (n=14). As such, extended heterogeneity in drug responsiveness was reflected by diverse degrees of alterations in cell cycle progression and apoptotic signalling, in addition to shifts in tumoral phenotypic states implying therapy-induced plasticity. A similar approach was used to measure drug activity in freshly resected tumour samples (n=18) harvested from different tumour regions (core or invasive front) within hours following surgery. Accordingly, we identified highly variable fractions of responsive tumour and microenvironmental cell populations in a patient-specific way. The ability to measure drug activity at single-cell resolution in a patient-tailored manner by applying a genotype-agnostic method, paves the way for advanced precision cancer medicine in GBM by offering a novel approach to more precisely select eligible patients for prospective clinical trials.

EXTH-20. SINGLE-CELL DRUG ACTIVITY MAPPING IN GLIOBLASTOMA IDENTIFIES EXTENDED DRUG RESPONSE HETEROGENEITY AND THERAPY-INDUCED CELLULAR PLASTICITY