KRAS mutation leads to resistance to combined RAF/EGFR and RAF/MEK inhibition. KRAS mutation leads to resistance to combined RAF/EGFR and RAF/MEK inhibition.

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Presentation transcript:

KRAS mutation leads to resistance to combined RAF/EGFR and RAF/MEK inhibition. KRAS mutation leads to resistance to combined RAF/EGFR and RAF/MEK inhibition. A, parental VACO432 cells (VACO) and derivatives made resistant to combined RAF/EGFR inhibition (VACO-RE) or RAF/MEK inhibition (VACO-RM) were treated for 3 days with the indicated concentrations of vemurafenib (VEM) and cetuximab (CET) or vemurafenib and selumetinib (SEL). Relative cell titer was determined by Cell TiterGlo assay. B, Sanger sequencing of exon 2 of KRAS from genomic DNA isolated from VACO, VACO-RE, and VACO-RM cells. WT, wild-type. C, VACO432 cells expressing exogenous KRASG12D, KRASG13D, or empty vector control were treated as in A, and relative cell titer was determined. D, VACO432 cells expressing KRASG12D, KRASG13D, or empty vector control were treated for 24 hours with the indicated concentrations of drugs, and Western blotting was performed with the indicated antibodies. E, VACO432 cells expressing exogenous KRASG12D, KRASG13D, or empty vector control were treated with the ERK inhibitor VX-11e (VX) as in A, and relative cell titer was determined. F, cells were treated as in D for 24 hours with the indicated concentrations of VX-11e, and Western blotting was performed with the indicated antibodies. Leanne G. Ahronian et al. Cancer Discovery 2015;5:358-367 ©2015 by American Association for Cancer Research