Mice were treated with rapamycin (3 mg/kg, 3x/week, i.p.), INK 128 (1mg/kg, 5x/week, p. o.), ganetespib (50mg/kg, 1x/week, i.v.) or in combination. Tumors were harvest and lysed 24h after ganetespib treatment and 6h after INK 128 or rapamycin treatment. Rapamycin treatment inhibited pS6K (Thr 389) and pS6 (Ser240/244) expression in the tumors. INK 128 treatment reduced pS6K (Thr 389), pS6 (Ser240/244), and p4E- BP1 isoform expression. Ganetespib reduced pS6K (Thr 389) and pS6 (Ser240/244) expression in some tumors. Combined ganetespib and rapamycin or INK 128 treatment showed a stronger inhibition of the mTOR pathway than each drug by itself. Rapamycin even inhibited pS6 (Ser240/244) expression in the liver. Abbreviations: c: cells from cell culture, v: vehicle, G: Ganetespib, I: INK 128, R: Rapamycin.