Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the paradigm of
treatment in non-small cell lung cancer (NSCLC). The molecular biology study of EGFR has led to clinical trials that select
patients more accurately, regarding the presence of EGFR activating mutations. Nonetheless, a lack of response or a
temporary condition of the response has been detected in patients on EGFR TKIs. This has urged to study potential resistance
mechanisms underneath. The most important ones are the presence of secondary mutations in EGFR, such as
T790M, or the overexpression of mesenchymal-epithelial transition factor (MET) that may explain why patients who initially
respond to EGFR TKIs, may ultimately become refractory. Several approaches have been taken and new drugs both
targeting EGFR resistance-mutation or MET are currently being developed. Here we review and update the EGFR biological
pathway as well as the clinical data leading to approval of the EGFR TKIs currently in the market. New compounds
under investigation targeting resistance mutations or dually targeting EGFR and other relevant receptors are also
reviewed and discussed.
Keywords: Activity mutations, epidermal growth factor receptor, tyrosine kinase inhibitors.
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