Acquired resistance to EGFR tyrosine kinase inhibitors in lung cancer.

摘要: Proc Amer Assoc Cancer Res, Volume 47, 2006 SY10-01 The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib (Iressa) and erlotinib (Tarceva), induce dramatic responses in certain patients with non-small cell lung cancer (NSCLC). Unfortunately, most who initially respond to these drugs eventually develop progression of disease. We previously reported that 2 5 clinically acquired resistance either or 1 patient progressed on adjuvant gefitinib, tumors contained a second site mutation the domain after progression, addition primary drug-sensitive EGFR (exon 19 deletion L858R point mutation) (Pao et al, PLoS Med ‘05b). The T790M amino acid change is predicted block binding drug ATP pocket via steric clash resulting from introduction bulky methionine residue. will present updated information more examined for mechanisms TKIs; such received as monotherapy combination chemotherapy. In addition, we are establishing tetracycline-inducible mouse models EGFR-dependent adenocarcinomas responsive (K Politi, M Zakowski, W Pao, H Varmus, manuscript preparation) resistant erlotinib. Such animals should be useful testing new strategies overcome clinic. acknowledge funding Joan's Legacy Foundation, Doris Duke Charitable NCI K08-CA097980-01A2, an anonymous donor.