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PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib.
Engelman JA, Zejnullahu K, Gale CM, Lifshits E, Gonzales AJ, Shimamura T, Zhao F, Vincent PW, Naumov GN, Bradner JE, Althaus IW, Gandhi L, Shapiro GI, Nelson JM, Heymach JV, Meyerson M, Wong KK, Jänne PA. Engelman JA, et al. Cancer Res. 2007 Dec 15;67(24):11924-32. doi: 10.1158/0008-5472.CAN-07-1885. Cancer Res. 2007. PMID: 18089823
MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling.
Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Jänne PA. Engelman JA, et al. Science. 2007 May 18;316(5827):1039-43. doi: 10.1126/science.1141478. Epub 2007 Apr 26. Science. 2007. PMID: 17463250