Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2019 Dec 27;9:19909. doi: 10.1038/s41598-019-56356-4

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Aurora kinase A as a potential therapeutic target in EGFR-mutant NSCLC resistant to olmutinib. (A) Summary of WES analysis in PDCs resistant to third-generation EGFR-TKIs. Known mechanisms of resistance to osimertinib are shown. (B) Inhibition of YU-1089 cells by gefitinib (IC₅₀ = 2,162 nmol/L), erlotinib (IC₅₀ = 1,231 nmol/L), afatinib (IC₅₀ = 275 nmol/L), dacomitinib (IC₅₀ = 244 nmol/L), neratinib (IC₅₀ = 275 nmol/L), olmutinib (IC₅₀ = 857 nmol/L), osimertinib (IC₅₀ = 1,013 nmol/L), and nazartinib (IC₅₀ = 3,908 nmol/L). Cell viability was measured by CellTiter-Glo. Data are presented as the mean ± SEM (n = 3). (C) YU-1089 cells were treated with the indicated concentrations of gefitinib, afatinib, or osimertinib for 6 hours. Cell lysates were immunoblotted with the indicated antibodies. Immunoblots are representative of 3 independent experiments. (D) Combinatorial drug screening with 1 μM of olmutinib and 1 μM of each kinase inhibitor from the drug library was performed on YU-1089 cells to identify potent drug combinations. The x axis represents a number of kinase inhibitors used in this screen. The y axis represents combination index (CI) determined by the Bliss independence model. Each dot is the resulting CI for the individual drug. Gray dots indicate drugs with antagonism (CI > 1), whereas black dots indicate drugs with synergism (CI < 1). Tozasertib (red) exhibited the strongest synergistic effect. The screening identified 41 drugs with synergistic effects (CI < 1). (E) YU-1089 cells were treated with olmutinib alone, tozasertib alone, or a combination of olmutinib with tozasertib for 2 weeks. Colony formation was stained by crystal violet (upper panel). The bar graph (lower panel) shows quantification of the crystal violet staining. (ANOVA with Dunnett’s post test: ***p < 0.001 vs the value in negative control, ^###p < 0.001 vs the value at the indicated comparison, n = 3). (F) YU-1089 cells were treated with the indicated concentrations of tozasertib or in combination with olmutinib for 24 hours. Cell lysates were immunoblotted with the indicated antibodies. Immunoblots are representative of 3 independent experiments. The full-length blots can be found in Supplementary Fig. 8.