Supplementary Figures 1-8 from Antitumor Activity of Osimertinib, an Irreversible Mutant-Selective EGFR Tyrosine Kinase Inhibitor, in NSCLC Harboring EGFR Exon 20 Insertions
Year: 2023
Type: supplementary-materials
Abstract: Supplementary figure 1: Generation of H2073 ASV and H2073 SVD. Supplementary figure 2: H2073 parental and Ex20Ins are dependent on EGFR for survival in vitro. Supplementary figure 3: Effect of TKI on the Sytox Proliferation of H2073 wt, H2073-SVD and H2073-ASV, in vitro. Supplementary figure 4: The H2073 parental NSCLC xenograft model is sensitive to afatinib in vivo. Supplementary figure 5: Osimertinib and AZ5104 given as monotherapy induce robust inhibition of p-EGFR and relevant downstream signalling pathways. Supplementary figure 6: Osimertinib and AZ5104 as monotherapy induce a strong inhibition of the level of pEGFR and the downstream signalling pathways. Supplementary figure 7: Osimertinib, AZ5104, afatinib and erlotinib are well tolerated at the dose explored in the PDX models and AZ5104 induce significant tumor growth inhibition in the LU0387 model when dosed at 50 mg/kg. Supplementary figure 8: Osimertinib, afatinib and erlotinib robustly inhibit pEGFR; however, select proteins representing downstream signalling pathways (pAKT) have enhanced inhibition to osimertinib and pS6R remains suppressed at early timepoints compared to afatinib and erlotinib in the UC Davis PDX model harboring the V769_D770InsASV.
Authors: Nicolas Floc'h, Matthew J. Martin, Jonathan W. Riess, Jonathan P. Orme, Anna D. Staniszewska, Ludovic Ménard, Maria Emanuela Cuomo, Daniel J. O'Neill, Richard A. Ward, M. Raymond V. Finlay, Darren McKerrecher, Mingshan Cheng, Daniel P. Vang, Rebekah A. Burich, James G. Keck, David R. Gandara, Philip C. Mack, Darren A.E. Cross
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4362609987