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Expression of Signaling Mediators Downstream of EGF-Receptor Predict Sensitivity to Small Molecule Inhibitors Directed Against the EGF-Receptor Pathway 

Published byMarie-Agnès Pageau Modified over 5 years ago

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Presentation on theme: "Expression of Signaling Mediators Downstream of EGF-Receptor Predict Sensitivity to Small Molecule Inhibitors Directed Against the EGF-Receptor Pathway "— Presentation transcript:

1 Expression of Signaling Mediators Downstream of EGF-Receptor Predict Sensitivity to Small Molecule Inhibitors Directed Against the EGF-Receptor Pathway  Martin L. Sos, MD, Thomas Zander, MD, Roman K. Thomas, MD, Andrea Staratschek-Jox, MD, Julia Claasen, Jürgen Wolf, MD  Journal of Thoracic Oncology  Volume 3, Issue 2, Pages (February 2008) DOI: /JTO.0b013e c05 Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

2 FIGURE 1 Different sensitivity of lung cancer cell lines to treatment with gefitinib. A, Exemplary viability data for H3255, H1975, and HCC44 where the relative viability (x axis) is displayed against the nanomolar concentration of a given compound (y axis). Similar results were obtained for the further 6 cell lines analyzed. B, Chemical structures of the reversible EGFR-TKI gefitinib and the 2 irreversible EGFR-TKI PD16,8393 and EKB C, Description of cell lines on histologic, mutational, and phenotypical level. Results of sequence analysis of EGFR exon 18–21 and KRAS. Scc, squamous cell carcinoma; bac, bronchioalveolar adenocarcinoma; ad, adenocarcinoma; n.d., not determined; D, To describe the sensitivity of a given cell line to an inhibitor, IC50-values (concentration needed to inhibit the viability of 50% of the cells) were calculated by fitting sigmoidal curves to the obtained data. The results for all screened cell lines and all inhibitors are displayed. Journal of Thoracic Oncology 2008 3, DOI: ( /JTO.0b013e c05) Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

3 FIGURE 2 Prediction of sensitivity of EGFR-TKI resistant cell lines to inhibition with different small molecules. A, Baseline expression of EGFR, PTEN, p-AKT, AKT, p-S6K, and S6K in all EGFR-TKI resistant cell lines. Actin expression was used as loading control. B, Hierarchical clustering of correlation coefficients (r2) of steady-state protein expression and sensitivity to a given inhibitor was performed for all EGFR-TKI resistant cell lines. Journal of Thoracic Oncology 2008 3, DOI: ( /JTO.0b013e c05) Copyright © 2008 International Association for the Study of Lung Cancer Terms and Conditions

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