PD and efficacy of AZD4785 in a KRAS wild-type lung cancer PDX model

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Fig. 2. Effects of AZD4785 on proliferation and MAPK pathway signaling in KRAS mutant and wild-type cancer cells in vitro. Effects of AZD4785 on proliferation.

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Differentiation of AZD4785 from MAPK pathway inhibitors in vitro

Fig. 1. Potent and selective down-regulation of KRAS mRNA and protein by AZD4785 in vitro and in vivo. Potent and selective down-regulation of KRAS mRNA.

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Differentiation of AZD4785 from MAPK pathway inhibitors in vitro

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Fig. 1. Potent and selective down-regulation of KRAS mRNA and protein by AZD4785 in vitro and in vivo. Potent and selective down-regulation of KRAS mRNA.

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Fig. 6. PD and efficacy of AZD4785 in a KRAS wild-type lung cancer PDX model. PD and efficacy of AZD4785 in a KRAS wild-type lung cancer PDX model. Mice bearing LXFA 526 tumors were treated with PBS, AZD4785, or CTRL ASO at 50 mpk 5× weekly. (A) KRAS and DUSP6 expression measured by qRT-PCR in the LXFA 526 tumors after 4 weeks of dosing. The expression is normalized to 18S rRNA and expressed relative to PBS. (B and C) KRAS protein expression measured by IHC in LXFA 526 tumors after 4 weeks of dosing. (B) Representative images are shown (scale bars, 100 μm) and (C) quantitation of KRAS (H score) determined by Image analysis platform. Data are the mean H score and SE. (D) AZD4785 showed modest inhibition of tumor growth versus PBS (51%; P = 0.001); however, there was no significant TGI compared to the CTRL ASO. Data shown are treatment group geometric mean and SE. (E) Surrogate endpoint survival graphs for the LXFA 526 study. Data are shown as the percentage of remaining animals with tumors <4× the initial starting volume in each treatment group. Sarah J. Ross et al., Sci Transl Med 2017;9:eaal5253 Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.