Strategies to overcome resistance to tyrosine kinase inhibitors in non-small-cell lung cancer

摘要: The use of molecularly targeted agents has dramatically improved the prognosis defined subsets patients with non-small-cell lung cancer harboring somatically activated oncogenes, such as mutant EGFR or rearranged ALK. However, after initial marked responses to ALK tyrosine kinase inhibitors (TKIs), almost all inevitably progress due development acquired resistance. Multiple molecular mechanisms resistance have been identified; best characterized are secondary mutations in domain oncogene, T790M and L1196M ALK, which prevent target inhibition by corresponding TKI. Other include copy number gain fusion gene activation bypass signaling pathways that can maintain downstream proliferation survival signals despite original drug target. Here, authors provide an overview known TKIs outline therapeutic strategies, including new i...