Management of tyrosine kinase inhibitor resistance in lung cancer with EGFR mutation

Abstract

The identification of driver mutations and drugs that inhibit their activity has been a major therapeutic advance for patients with advanced lung adenocarcinoma. Unfortunately, the success of these drugs is limited by the universal development of resistance. Treatment failure can result from inadequate drug exposure or selection of resistant malignant clones. Clinically distinct mechanisms of disease progression have been identified and can inform treatment decisions. Investigations into the biochemical mechanisms of tyrosine kinase inhibitor resistance may provide additional therapeutic targets by which the efficacy of targeted therapy can be improved.

Keywords: Epidermal growth factor receptor mutation; Tyrosine kinase inhibitor; Lung cancer; Adenocarcinoma; Resistance; Targeted therapy

Core tip: The causes of epidermal growth factor receptor tyrosine kinase inhibitor (TKI) treatment failure including pharmacokinetic failure, intrinsic resistance and acquired resistance are discussed. We review the molecular mechanisms of resistance and the options for clinical management of disease progression. Promising investigational strategies for overcoming TKI resistance are highlighted.