Overcoming crizotinib resistance in ALK-rearranged NSCLC with the second-generation ALK-inhibitor ceritinib

被引：40

作者：

Muller, Ittai B. ^{[1
]}

De Langen, Adrianus J. ^{[2
]}

Honeywell, Richard J. ^{[1
]}

Giovannetti, Elisa ^{[1
,3
]}

Peters, Godefridus J. ^{[1
]}

机构：

[1] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, POB 7057, NL-1007 MB Amsterdam, Netherlands

[2] Vrije Univ Amsterdam Med Ctr, Dept Med Pulmonol, NL-1007 MB Amsterdam, Netherlands

[3] DIPINT, AIRC Startup Unit, Canc Pharmacol Lab, Pisa, Italy

来源：

EXPERT REVIEW OF ANTICANCER THERAPY | 2016年 / 16卷 / 02期

关键词：

resistance mutation. EML-ALK; anaplastic lymphoma kinase; ceritinib; Acquired resistance; tyrosine kinase inhibitors; crizotinib; CELL LUNG-CANCER; MULTICENTER PHASE-II; ADULT PATIENTS PTS; KINASE INHIBITOR; ACQUIRED-RESISTANCE; SINGLE-ARM; OPEN-LABEL; BRAIN METASTASES; POTENT; EGFR;

D O I：

10.1586/14737140.2016.1131612

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In up to 5% of non-small cell lung cancer (NSCLC) patients, the EML4-ALK translocation drives tumor progression. Treatment with the ALK inhibitor crizotinib is more effective than standard chemotherapy. However, resistance to crizotinib occurs after approximately 8months. Ceritinib is the first second-generation ALK inhibitor approved for treatment of crizotinib-resistant NSCLC. Ceritinib inhibits two of the most common ALK-mutants that confer resistance to crizotinib: L1196M and G1269A. Cells with ALK expression are more sensitive to ceritinib than crizotinib (IC50 25 nM vs. 150 nM, respectively). Alternative second-generation ALK inhibitors such as Alectinib, Brigatinib and PF-06463922 are currently in development, each affecting different crizotinib-resistant ALK target mutations. Genetic identification of crizotinib-resistant mutants is essential for selecting the optimal treatment strategy in NSCLC patients to overcome resistance and to increase progression-free survival.

引用

页码：147 / 157

页数：11

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