Fig. 4

Unsupervised hierarchical clustering of drug sensitivity patterns in primary GBM and relation to subtype and MGMT status. Heat map and unsupervised hierarchical clustering of patient-specific drug responses (sDSS) with Euclidian distance (cultures and drugs). The heat map is filtered by DSS ≥10 and sDSS ≥ or ≤ 6.5 (n = 74 drugs). The two most sensitive cultures clustered separately and were both of a proneural subtype, with a methylated MGMT promoter. The four least sensitive cultures grouped together in the other major taxonomy; however, among the moderate and least sensitive cultures, no clear pattern was observed in the subtype classification or methylation status of the parent tumor. Even in the cultures clustering together, individual differences in sensitivities to different mechanistic classes of drugs were found (e.g., sensitivity to topoisomerase I inhibitors in T1459 compared to that in T1506, sensitivity to CDK-inhibitors in T1549 compared to that in T1561, sensitivity to mTOR-pathway inhibitors in T1456 compared to that in T1502, and sensitivity to MEK1/2 inhibitors in T1461 compared to that in T1550). Subtype; M: Mesenchymal, PN: proneural, gray box: not available data. MGMT promoter status: ME: Methylated MGMT promoter, UN: Unmethylated MGMT promoter, gray box: not available data