Mechanisms of resistance to EGFR tyrosine kinase inhibitors gefitinib/erlotinib and to ALK inhibitor crizotinib

作者：Tartarone Alfredo^*; Lazzari Chiara; Lerose Rosa; Conteduca Vincenza; Improta Giuseppina; Zupa Angela; Bulotta Alessandra; Aieta Michele; Gregorc Vanesa

来源：Lung Cancer, 2013, 81(3): 328-336.

DOI：10.1016/j.lungcan.2013.05.020

• Non small cell lung cancer
• Epidermal growth factor receptor
• ALK translocation
• Primary and acquired resistance to EGFR-TKIs
• Resistance to crizotinib
• Targeted therapy

The discovery of several molecular alterations that underlie non-small cell lung cancer (NSCLC) pathogenesis has led to the development of targeted therapies. In particular, gefitinib and erlotinib have become the standard of care in patients harboring epidermal growth factor receptor mutations, while crizotinib showed an impressive efficacy in patients with ALK-positive NSCLC. Nevertheless, the occurrence of clinical resistance limits the long term results of these novel agents. The identification of the molecular mechanisms responsible for acquired resistance to targeted therapy is crucial in order to pursue the creation of rational strategies to overcome resistance. In the current review, we will focus on the acquired resistance mechanisms to EGFR-TKIs and crizotinib and the therapeutic strategies currently under study to overcome resistance.

• 出版日期2013-9