Third-Generation Tyrosine Kinase inhibitors Targeting epidermal Growth Factor Receptor Mutations in non-Small Cell Lung Cancer

被引:47
作者
Barnes, Tristan A. [1 ]
O'Kane, Grainne M. [1 ]
Vincent, Mark David [2 ]
Leighl, Natasha B. [1 ]
机构
[1] Princess Margaret Canc Ctr, Dept Med Oncol, Toronto, ON, Canada
[2] London Reg Canc Ctr, Dept Med Oncol, London, ON, Canada
关键词
lung cancer; lung cancer treatment; epidermal growth factor receptor; tyrosine kinase inhibitors; T790M; IRREVERSIBLE EGFR INHIBITOR; ACQUIRED-RESISTANCE; 1ST-LINE TREATMENT; BRAIN METASTASES; OPEN-LABEL; C797S MUTATION; GENE-MUTATIONS; ACTIVATING MUTATIONS; OSIMERTINIB AZD9291; NEVER-SMOKERS;
D O I
10.3389/fonc.2017.00113
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Sensitizing mutations in the epidermal growth factor receptor (EGFR) predict response to EGFR tyrosine kinase inhibitors (TKIs) and both first-and second-generation TKIs are available as first-line treatment options in patients with advanced EGFR-mutant non-small cell lung cancer. Eventual resistance develops with multiple mechanisms identifiable both upon repeat biopsy and in plasma circulating tumor DNA. The T790M gatekeeper mutation is responsible for almost 60% of cases. A number of third-generation TKIs are in clinical development, and osimertinib has been approved by the US Food and Drug Administration for the treatment of patients with EGFR T790M mutant lung cancer after failure of initial EGFR kinase therapy. Resistance mechanisms are being identified to these novel agents, and the treatment landscape of EGFR-mutant lung cancer continues to evolve. The sequence of EGFR TKIs may change in the future and combination therapies targeting resistance appear highly promising.
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页数:9
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