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. 2021 Nov 25;4:1333. doi: 10.1038/s42003-021-02842-3

Fig. 8. Trametinib becomes effective in Ras-driven pancreatic tumours when these are forced into a temporary state of interactome hyperconnectivity.

Fig. 8

a Schematic of the experimental design and the expected outcome of the PU-induced interactome hyperconnectivity. b Native-PAGE shows epichaperome levels and SDS-PAGE signalling activity in individual tumours (n = 3 from each cohort as in (a)). See also Supplementary Fig. 5. c Epichaperome levels in MiaPaCa2 tumours and signalling activity in PDX PC46 tumours. Error bars mean ± SEM; unpaired two-tailed t test. d The anti-tumour activity of Trametinib (Tb) when tumours are forced into a state of interactome hyperconnectivity by PU-H71 (PU) given on Monday, each week. Tb is administered then daily, 24 h after PU. PU- > Tb, PU (75 mg kg−1) given on the first day followed 24 h later by Tb (1 mg kg−1) given on the next four consecutive days; Vehicle (Control); PU-H71 (75 mg kg−1, PU) given once per week; Trametinib (1 mg kg−1, Tb) given on four consecutive days. Pooled from 2 independent experiment, n = 14 and 3 mice for Vehicle; 12 and 4 mice for PU; 12 and 4 mice for Tb; 10 and 3 mice for PU- > Tb, in MiaPaCa2 CDX and PC46 PDX tumours, respectively. Error bars mean ± SEM; unpaired two-tailed t-test. e Body weight of each cohort as in (a). Graph, mean ± SEM.