AMG232 and irradiation treatment of patient-derived GBM cell lines

Patient-derived GBM cell lines were acutely treated in vitro with AMG232 and radiotherapy (RT), after which we measured the changes in drug-relevant and GBM phenotypic markers between control and treated samples. In parallel, on the same cell line pool, we performed bulk cytotoxicity assays, where we tested the long-term survival of the cell lines. Finally, we used the expression changes of the protein markers and correlated them to the sensitivity profiles, to ultimately generate a predictive model.
Conclusion:
As in the bulk dose-response assays, at the protein level, we saw that TP53 wild type cells were more sensitive to the therapies than TP53 mutant cells. However, there was heterogeneous response potential within the TP53 wild type pool. As such, we learned that drug-response markers induced upon drug treatment, an approach called functional diagnostics is more predictive of in vitro cell survival outcome, than baseline protein expression levels.
Notes:
All samples were barcoded, pooled, stained and analysed in a single experiment. Cytotoxicity