Fig. 5: Cotargeting mediator kinase prevents resistance to ERK/MAPK inhibition.
a Bar chart depicting the time at which resistance emerged to treatment with either SCH772984 (1 µM) alone or SCH772984 (1 µM) in combination with Senexin A (1 µM). b Oncoplot of three rectal cancer tumoroids based on MSK-IMPACT testing (top), with representative micrographs below of RC-MSK-001 patient tumor (left) and its corresponding tumoroid (right). c TTP assays for rectal cancer tumoroids treated with SCH772984 (100 nM) alone or in combination with Senexin A (1 µM). d Relative viability of rectal cancer tumoroids treated with Senexin A (1 µM) compared to DMSO (1:1000) for 14 days. e Crystal violet staining of 14 day colony growth of 2.1.1syn_Luc cells treated with the indicated drug combinations. Box plot demonstrating whole body luminescence (f) and tumor weights (g) after orthotopic implantation of 103 2.1.1syn_Luc cells into FVB/n mice and treatment with SCH772984 (35 mg/kg) in combination with or without CCT251545 (75 mg/kg) for 21 days, 10 mice per group. g Mean mouse weights throughout treatment described in Fig. 5f, g. Error bars represent standard deviations.
