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. Author manuscript; available in PMC: 2022 Sep 28.
Published in final edited form as: Sci Transl Med. 2022 Mar 30;14(638):eabc7480. doi: 10.1126/scitranslmed.abc7480

Figure 4: Targeted therapy-induced ATM activation and targeting in vivo.

Figure 4:

A. Tumor volume (normalized to t=0, %) of PC9 cell line xenografts in nude mice following treatment with vehicle, osimertinib, AZD0156, or the combination for indicated time points (n=5 mice in each treatment arm). P values were determined using unpaired, two-tailed Student’s t-test. B. Fold change in individual tumor volume (normalized to t=0) for PC9 tumors treated with osimertinib or the combination of osimertinib and AZD0156. C. Tumor volume (normalized to t=0, %) of H1975 cell line xenografts in nude mice following treatment with vehicle, osimertinib, AZD0156, or the combination for indicated time points (n=4–5 mice in each treatment arm). P values were determined using unpaired, two-tailed Student’s t-tests. D. Fold change in individual tumor volume (normalized to t=0) for H1975 tumors treated with osimertinib or the combination of osimertinib and AZD0156. E. Tumor volume (normalized to t=0, %) of MGH134 patient-derived cell line xenografts in nude mice following treatment with vehicle, osimertinib, AZD0156, or the combination for indicated time points (n=9–10 mice in each treatment arm). P values were determined using unpaired, two-tailed Student’s t-tests. F. Fold change in individual tumor volume (normalized to t=0) for MGH134 tumors treated with osimertinib or the combination of osimertinib and AZD0156. G. p-ATM IHC score of patient tumor tissue obtained before (treatment naïve, TN) or during treatment with erlotinib (progressive disease, PD). Same numbers indicate tumors longitudinally sampled from the same patient. H. Representative image of p-ATM IHC from patient tumors before treatment (treatment naïve) or during treatment (progressive disease). Images taken at 20x magnification. I. p-ATM IHC scores from 5 matched tumor samples from patients with EGFR mutant lung adenocarcinoma taken at the time of diagnosis and at the time of relapse to EGFR inhibitor erlotinib. P values were determined using unpaired, two-tailed Student’s t-tests. J. Proposed model of ATM dependence in targeted therapy treated tumors, leading to rational combination of targeted therapies and ATM inhibitors.