Fig. 2

High-throughput combination drug screening identified palbociclib-based drug-drug interactions in HNSCC. a Schematic layout of the palbociclib screening versus 162 different compounds. Top: each drug pair was tested in a 6 × 6 matrix block, with five doses plus DMSO control. Bottom: examples of percent response and ∆Bliss heat maps for additivity, synergy, or antagonism outcomes. b The hierarchal view of drug screening was ranked by synergy, as assessed by the average ExcessHSA metric. Top colorful bars highlight drugs from key mechanistic classes, including PI3K/AKT/mTOR (red), EGFR (blue), MEK (orange), BRD4 (purple) inhibitors, fluorouracil (light green), nedaplatin (light brown), cisplatin (dark blue), docetaxel (black), and paclitaxel (grey). The numbers in brackets represent the number of inhibitors in top 20 synergistic compounds. c Individual ExcessHSA values of palbociclib combined with 13 PI3K pathway inhibitors from the screening library that were classified as PI3K isoform (blue), AKT (green), and mTOR (red) inhibitors. d Bar plot showing the ExcessHSA in different kinds of PI3K pathway. Data are shown as the mean ± SD. *P < 0.05 and *** P < 0.001, as estimated by two-way ANOVA. e The 10×10 heat maps of % Response and ∆ Bliss palbociclib combinations with pictilisib, alpelisib, taselisib (GDC-0032), or apitolisib in FADU. f The ExcessHSA values for palbociclib combination with the four PI3K inhibitors shown in e. Data are shown as the mean ± SD. ns, not significant, as estimated by two-way ANOVA