Fig. 2

Probabilistic Target Inhibition Maps (PTIMs) and experimental in vitro and in vivo results for U23674 alveolar rhabdomyosarcoma (aRMS) drug combinations. Targets with adjacent asterisks indicate targets selected for in vitro validation. Values in the center of PTIM blocks represent expected scaled sensitivity following inhibition of associated block targets. a Abbreviated baseline chemical screen-informed PTIM. b Abbreviated chemical screen RNA-seq + informed PTIM. c Abbreviated chemical screen + exome-seq informed PTIM. The values within the target blocks indicate scaled drug sensitivity for the given target combination [16] when the targets are inhibited via one or more chemical compounds. More information can be found in prior publications [16, 18]. In (d-e), results are based on n = 3 technical replicates with n = 4 replicates per treatment condition. d Dose response curve for OSI-906 varied dosage + GDC-0941 fixed dosage. The response for GDC-0941 at varied dosages is included. e Dose response curve for GDC-0941 varied dosage + OSI-906 fixed dosage. The response for OSI-906 at varied dosages is included. f Schematic representation of in vivo experiment design. g Kaplan-Meier survival curves for in vivo orthotropic mouse experiment. Mice were treated with vehicle (n = 8 mice, black line), 50 mg/kg OSI-906 (n = 8 mice, blue line), 150 mg/kg GDC-0941 (n = 7 mice, red line), or combination 50 mg/kg OSI-906 + 150 mg/kg GDC-0941 (n = 8 mice, purple line). The medicine bottle image is public domain, provided by user Kim via clker.com (http://www.clker.com/clipart-blank-pill-bottle-3.html)