Crizotinib in ROS1-positive non-small cell lung cancer: an Asian large phase II trial confirms its key-role

Paolo Maione, Cesare Gridelli


The ROS1 oncogene encodes an orphan receptor tyrosine kinase related to anaplastic lymphoma kinase (ALK), along with members of the insulin-receptor family (1). ROS1 rearrangement can be found in several human cancers as cholangiocarcinoma, gastric cancer, ovarian cancer, glioblastoma multiforme, and with therapeutic implications in non-small cell lung cancer (NSCLC) (2-4). As a consequence of the rearrangement, a portion of ROS1, that includes the entire tyrosine kinase domain, is fused with 1 of 12 different pattern proteins (5). The ROS1 fusion kinases resulting from rearrangement are constitutively activated and drive cellular neoplastic transformation.