Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab.

摘要: The epidermal growth factor receptor (EGFR) is a ubiquitously expressed tyrosine kinase (RTK) and recognized as key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used oncology, two monoclonal antibodies (panitumumab, cetuximab) three (erlotinib, gefitinib, lapatinib). Both strategies inhibition have demonstrated clinical successes, however tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms acquired to cetuximab we previously established series cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line escalating doses cetuximab. Cetuximab-resistant exhibited dramatic increase steady-state expression EGFR, HER2, HER3 receptors well increased signaling through MAPK AKT pathways. RNAi studies dependence on network. These findings prompted investigation whether not cells with would be sensitive targeted TKI erlotinib. In vitro, erlotinib was able decrease axis, cellular proliferation, induce apoptosis. determine if could therapeutic benefit vivo, mouse xenografts, subsequently treated them Mice harboring either tumor regression delay compared vehicle controls. Analysis proliferation rates work presented herein suggests that 1) maintain their 2) developing can from subsequent treatment erlotinib, providing rationale for its use setting resistance.