Chapter title |
Crizotinib
|
---|---|
Chapter number | 4 |
Book title |
Small Molecules in Oncology
|
Published in |
Recent results in cancer research Fortschritte der Krebsforschung Progrès dans les recherches sur le cancer, January 2018
|
DOI | 10.1007/978-3-319-91442-8_4 |
Pubmed ID | |
Book ISBNs |
978-3-31-991441-1, 978-3-31-991442-8
|
Authors |
David F. Heigener, Martin Reck, Heigener, David F., Reck, Martin |
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. |
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Demographic breakdown
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Student > Master | 14 | 14% |
Student > Bachelor | 12 | 12% |
Student > Ph. D. Student | 8 | 8% |
Other | 6 | 6% |
Other | 12 | 12% |
Unknown | 31 | 32% |
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Other | 3 | 3% |
Unknown | 33 | 34% |