Fig. 6: CDK2 loss drives resistance to pharmacological inhibitors.

A DrugZ analysis from HCC1806 and MIA PaCa-2 cells identified CDK2 was positively selected following INX-315 treatment. B Impact of INX-315 on the normalized counts of individual guides that target CDK2 from HCC1806 and MiaPaCa-2 cell lines. C Live cell imaging to monitor the proliferation of MCF7 cells following the depletion of CDK2 in the absence and presence of INX-315 (500 nM). Statistical significance was compared between siNT+INX-315 and siCDK2+INX-315. D Cell cycle analysis in MIA PaCa-2 cells following CDK2 depletion in the absence and presence of INX-315 up to 48 h. Error bar represents mean and SEM from n = 3 independent experiments. E Biochemical analysis from MCF7 and MiaPaCa-2 cells on the indicated proteins following CDK2 knockdown in the absence and presence of INX-315. Western blotting was done at two independent times. F Differential effect of INX-315 in MCF7-sgCtrl, MCF7-sgCDK2, MiaPaCa-2-sgCtrl, MiaPaCa-2-sgCDK2, 3226-sgCtrl and 3226-sgCDK2 cells following the treatment with INX-315. Statistical significance was compared between siNT+INX-315 and siCDK2+INX-315 sgCtrl+INX-315 and sgCDK2+INX-315. G Differential effect of PF-07104091 in 3226 sgCtrl and 3226 sgCDK2 cell lines based on live cell imaging. Statistical significance was compared between siNT+INX-315 and siCDK2+INX-315, sgCtrl+PF-07104091 and sgCDK2+PF-07104091. H Cell cycle analysis in MCF7 sg Ctrl and MCF7 sgCDK2 following the treatment with INX-315 and PF-07104091. I Effect of INX-315 on the cell cycle profiles of 3226 sg Ctrl and 3226 sg CDK2. J PI profile from 3226 sg Ctrl and 3226 sg CDK2 cells following the treatment with RO-3306 for 48 h. Experiments were done three independent times. *** represents p value < 0.0001 as determined by 2-way ANOVA for (C, F & G). Source data are provided as a source data file.