Recent Results Cancer Res. 2018;211:57-65. doi: 10.1007/978-3-319-91442-8_4.


Crizotinib is an ATP-competitive small-molecule inhibitor of the receptor tyrosine kinases (RTK) C-Met, ALK and ROS1. There is a robust effectiveness in non-small-cell lung cancer (NSCLC) harbouring EML4-ALK-rearrangements resulting in constitutional activation of the ALK-RTK. The drug is approved for this entity, which represents no more than 3-5% of all NSCLC. However, in this population, impressive response rates are generated. The same is true for ROS-1 rearrangements; however, these only occur in approximately 1% of all NSCLC. In small series, efficacy is also reported in patients, whose tumours harbour a MET Exon 4 skipping mutation (approx. 3% of all NSCLC). Toxicities include visual impairment, nausea, peripheral edema, QT-prolongation and liver-enzyme elevation. Also, the occurrence of renal cysts is reported. The detection of ALK-protein by immunohistochemistry is a predictor of efficacy for crizotinib. In cases of doubt, fluorescence in situ hybridisation (FISH) detecting the ALK-rearrangement has to be performed on tumour tissue. FISH is also the method of choice to detect ROS1-rearrangement, whereas MET-mutations are detected by sequencing methods. The high efficacy of crizotinib in ALK- and ROS-rearranged as well as MET mutated lung cancer as new molecular targets beside the epidermal growth factor receptor (EGFR) underscores the importance of molecular typing in NSCLC.

Keywords: ALK-Rearrangement; C-MET; Crizotinib; ROS-1.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Crizotinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Neoplasms / drug therapy
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / pharmacology*
  • Pyridines / pharmacology*


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib