Lorlatinib is a 3rd generation macrocyclic ALK inhibitor that shows significant improvement of inhibition against ROS1 kinase over 2nd generation inhibitors. Several cancers, when treated by ALK inhibitors, eventually develop point mutations, making the treatment ineffective. In a glioblastoma tumor model genetically engineered to reproduce ROS1 mutation, lorlatinib was yet able to demonstrate anticancer activity. Lorlatinib has also been shown to be effective as a single agent treatment on a mouse model of neuroblastoma. In addition, PET studies have found that lorlatinib successfully penetrates the blood-brain barrier resulting in high brain permeability of this inhibitor.