Extended Data Fig. 3: Analysis was ran on tissues collected from mice in Fig. 3.
From: Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer
(a) Quantification of phospho-ERKT202/Y204 IHC staining of tumors isolated from Vehicle and RMC-7977-treated KPF/FC mice, at indicated timepoints post single dose. (b) qRT-PCR analysis was ran on tumors collected from KPF/FC mice treated with a single dose of Vehicle or RMC-7977 (50mg/kg). Plot shows relative expression of five MAPK pathway signature genes over time. Results were compared by two-tailed Student’s unpaired t-test (*, p < 0.05; **, p < 0.01; p < 0.001; ****, p < 0.0001). Error bars indicate ±s.d. (c,d) PK/PD in the colons and skin isolated from CDX tumor-bearing mice. Pharmacokinetic response shown as RMC-7977 concentration in (c) colon and (d) skin (solid blue lines) over time. Pharmacodynamic response shown as relative change in Dusp6 expression in colon or skin (red solid lines) over time. Shades of blue or red represent three tested doses. Error bars indicate ±s.d. (e) Quantification of phospho-ERKT202/Y204 IHC staining of colons isolated from Vehicle and RMC-7977-treated KPF/FC mice, at indicated timepoints post single dose. (f) PK/PD of RMC-7977 in the colons isolated from KPF/FC mice. Pharmacokinetic response shown as RMC-7977 concentration in colon (solid blue lines) over time. Pharmacodynamic response shown as relative change in phospho-ERKT202/Y204 positive IHC staining (red solid lines) over time. Shades of blue or red represent three tested doses. Error bars indicate ±s.d. (a,e) Analysis of IHC images based on 10 fields of view and plotted as average per tissue section. Shades of blue represent three tested doses. Results were compared by two-tailed Student’s unpaired t-test (*, p < 0.05; **, p < 0.01; ****, p < 0.0001).