TY - JOUR
T1 - Mechanisms of resistance to EGFR tyrosine kinase inhibitors gefitinib/erlotinib and to ALK inhibitor crizotinib
AU - Tartarone, Alfredo
AU - Lazzari, Chiara
AU - Lerose, Rosa
AU - Conteduca, Vincenza
AU - Improta, Giuseppina
AU - Zupa, Angela
AU - Bulotta, Alessandra
AU - Aieta, Michele
AU - Gregorc, Vanesa
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - ALK translocation
KW - Epidermal growth factor receptor
KW - Non small cell lung cancer
KW - Primary and acquired resistance to EGFR-TKIs
KW - Resistance to crizotinib
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=84881660855&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881660855&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2013.05.020
DO - 10.1016/j.lungcan.2013.05.020
M3 - Article
C2 - 23809060
AN - SCOPUS:84881660855
VL - 81
SP - 328
EP - 336
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
IS - 3
ER -