Fig. 11

CHK1 inhibitors synergic effects with palbociclib and abemaciclib in Y537S cells. A Kaplan–Meier plots showing the relapse-free survival (RFS) probability in women carrying breast tumors expressing ERα, PR, or both expressing or not HER2 as a function of CHK1 mRNA levels. All possible cutoff values between the lower and upper quartiles are automatically computed (i.e., auto select best cutoff on the website), and the best performing threshold is used as a cutoff [27]. Details of the parameters of the curves are given in supplementary table 3. Significant differences between the RFS are given as p-value in each panel. B mRNA expression levels of CHK1 and CHK2 in patient-derived xenograft (PDX) immortalized cell lines stratified as indicated in the graph. Data have been extracted by the supplementary materials given in [43] . Volcano plot showing the mRNA expression as a function of the p-value of the indicated proteins (i.e., presenilin2 -pS2, TFF—red, CHK1 – blue) in CRISPR/CAS9 engineered MCF-7 cells expressing the Y537S (C) or the D538G (D) ERα mutant as extracted by the supplementary materials given in [44]. Synergy map of 5 days-treated Y537S cells with different doses of MK8776 (MK) (E) or prexasertib (Prexa) and palbociclib (Palbo) or abemaciclib (Abe) (E and F left and right panels, respectively). Significant differences with respect to untreated (i.e., -,-) samples are calculated by Student t-test and indicated by **** p-value < 0.0001. Significant differences between MK + Abe with respect to MK alone or Abe alone are calculated by Student t-test and indicated by °°°° p-value < 0.0001. Significant differences between MK + Palbo with respect to MK alone or Palbo alone are calculated by Student t-test and indicated by ^^^^ p-value < 0.0001. Significant differences between Prexa + Abe with respect to Prexa alone or Abe alone are calculated by Student t-test and indicated by °°°° p-value < 0.0001. Significant differences between Prexa + Palbo with respect to Prexa alone or Palbo alone are calculated by Student t-test and indicated by ^^^^ p-value < 0.0001. Growth curves in Y537S cells showing the synergic effect of each combination of compounds with selected doses are shown in (E’ and F’). For details, please see the material and methods section