Fig. 9

In vivo targeted treatment tests. a, b CET-sensitive models with increased baseline GF expression were treated with the indicated mono- or combination therapy aiming at response optimization and delay of SR development. *, each star represents a tumor that was taken out due to weight loss of the mouse. c Individual growth curves for tumors under either CET mono- or CET-trametinib combination therapy from panel a. d–g The indicated CET SR models were treated with the indicated mono- or combination therapy addressing identified SR mechanisms. PD, progressive disease; PR partial response; gray shaded area, stable disease. h Representative immunoblots of total STAT3 protein expression and phosphorylation of STAT3 at Y705 [pSTAT3 (Y705)]. K, untreated BoC32 tumors; 5dC, tumors treated for 5 days with CET; C, tumors which developed SR under chronic CET treatment (left panel) as well SR tumors treated with the indicated mono- or combination therapy (right panel). i Relative quantification of the indicated protein signal intensities to the corresponding intensities of the control tumor normalized with the corresponding beta-actin signal intensities using Image Lab (BioRad). Relative growth curves are derived from mean values ± SEM (error bars); V, Vorinostat; R, Ruxolitinib. j The BoC32 CET SR model with high pSTAT3 was treated with the indicated mono- or combination therapy addressing activated STAT3 signaling