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Crizotinib

  • David F. Heigener
  • Martin Reck
Chapter
First Online:
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 211)

Abstract

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

Crizotinib ALK-Rearrangement C-MET ROS-1 
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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Thoracic OncologyLungenClinic GrosshansdorfGrosshansdorfGermany

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