Next-Generation Covalent Irreversible Kinase Inhibitors in NSCLC: Focus on Afatinib.

ABSTRACT: First-generation, reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, represented an important addition to the treatment armamentarium for non-small-cell lung cancer (NSCLC) patients with activating EGFR mutations. However, all patients inevitably develop acquired resistance to these agents, primarily due to secondary EGFR mutations, molecular aberrations affecting other signaling pathways, or transformation to small-cell histology. It was hypothesized that development of second-generation TKIs with broader inhibitory profiles could confer longer-lasting clinical activity and overcome acquired resistance to first-generation inhibitors. Here, we review the development of afatinib, an irreversible ErbB family blocker that potently in

SUBMITTER: Hirsh V 

PROVIDER: S-EPMC4488453 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature