TY - JOUR
T1 - Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC)
T2 - Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies
AU - D'Angelo, Alberto
AU - Sobhani, Navid
AU - Chapman, Robert
AU - Bagby, Stefan
AU - Bortoletti, Carlotta
AU - Traversini, Mirko
AU - Ferrari, Katia
AU - Voltolini, Luca
AU - Darlow, Jacob
AU - Roviello, Giandomenico
PY - 2020/11/6
Y1 - 2020/11/6
N2 - The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies.
AB - The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies.
U2 - 10.3390/cancers12113293
DO - 10.3390/cancers12113293
M3 - Review article
C2 - 33172113
SN - 2072-6694
VL - 12
JO - Cancers
JF - Cancers
IS - 11
M1 - 3293
ER -
