Abstract:
:Discovery of activating mutations in epidermal growth factor receptor (EGFR) as a predictive biomarker for first-generation EGFR tyrosine kinase inhibitors (TKIs) has initiated an era of precision oncology for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). Despite the robust efficacy of first- and second-generation EGFR TKIs, disease relapse is inevitable. EGFR T790M mutation is the predominant cause of disease relapse and third-generation, irreversible EGFR inhibitors designed for targeting EGFR T790M and activating mutations have demonstrated promising clinical activity and tolerability. Unfortunately, disease progression inevitably occurs and heterogenous resistance mechanisms have been reported with limited subsequent treatment strategies available. Till now, treatment approaches for patients progressed from third-generation EGFR TKIs have not been clearly established. In this review, we summarize the recent findings in resistance mechanisms to third-generation EGFR TKIs and emerging treatment approaches for EGFR-mutant patients after resistance to third-generation EGFR TKIs. We further discuss clinical challenges and future perspectives for management of EGFR-mutant patients resistant to third-generation EGFR TKIs.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Zhang YC,Zhou Q,Wu YLdoi
10.1016/j.canlet.2019.05.044subject
Has Abstractpub_date
2019-09-10 00:00:00pages
240-247eissn
0304-3835issn
1872-7980pii
S0304-3835(19)30346-5journal_volume
459pub_type
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