The ALK Inhibitor Ceritinib Overcomes Crizotinib Resistance in Non–Small Cell Lung Cancer
Genomics Institute of the Novartis Research Foundation · Harvard University · +2 more institutions
Abstract
UNLABELLED: Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to the ALK tyrosine kinase inhibitor (TKI) crizotinib. Herein, we report the first preclinical evaluation of the next-generation ALK TKI, ceritinib (LDK378), in the setting of crizotinib resistance. An interrogation of in vitro and in vivo models of acquired resistance to crizotinib, including cell lines established from biopsies of patients with crizotinib-resistant NSCLC, revealed that ceritinib potently overcomes crizotinib-resistant mutations. In particular, ceritinib effectively inhibits ALK harboring L1196M, G1269A, I1171T, and S1206Y mutations, and a cocrystal…
Citation impact
- FWCI
- 86.53
- Percentile
- 100%
- References
- 19
Authors
24- LFLuc Friboulet
Genomics Institute of the Novartis Research Foundation, Harvard University, Massachusetts General Hospital, Japanese Foundation For Cancer Research
- NLNanxin Li
Genomics Institute of the Novartis Research Foundation, Harvard University, Massachusetts General Hospital, Japanese Foundation For Cancer Research
- RKRyohei Katayama
Genomics Institute of the Novartis Research Foundation, Harvard University, Japanese Foundation For Cancer Research
- CCChristian C. Lee
Genomics Institute of the Novartis Research Foundation, Harvard University, Massachusetts General Hospital, Japanese Foundation For Cancer Research
- JFJustin F. Gainor
Genomics Institute of the Novartis Research Foundation, Harvard University, Massachusetts General Hospital, Japanese Foundation For Cancer Research
Topics & keywords
- Crizotinib
- Ceritinib
- Anaplastic lymphoma kinase
- ALK inhibitor
- Lung cancer
- Cancer research
- Acquired resistance
- Medicine
- Good health and well-being