TKI Resistance for T790M Mutation
10.3779/j.issn.1009-3419.2015.04.10
- VernacularTitle:TKI耐药后针对T790M突变治疗
- Author:
WANG HONG
1
;
GUO RUI
;
ZHANG LIYU
Author Information
1. 中国人民解放军307医院肺部肿瘤科
- Keywords:
Epidermal growth factor receptor;
Tyrosine kinase inhibitors;
Lung neoplasms;
TKI resistance;
T790M;
Afatinib;
Dacomitinib;
Erlotinib;
Geiftinib
- From:
Chinese Journal of Lung Cancer
2015;18(4):245-250
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Epidermal growth factor receptor (EGFR) the development of orally ac-tivesmall molecule inhibitors for non-small cell lung cancer (NSCLC) provides anew treatment plan.EGFR gene mutation in patients with activation EGFR tyrosine kinase inhibitor (EGFR-TKIs) therapy for the treatment of sensitive, so that a large number of clinical beneift. The ifrst generation of reversible ATP-competitive EGFR-TKIs, geiftinib and erlotinib as ifrst-line, second-line or has the effect of maintenance therapy. Although the initial effect of these drugs have, but most patients will pro-duce drug resistance. Within a year, 50%-60% patients had T790M housekeeping gene mutation associated with. Irreversible EGFR-TKIs recent background: afatinib and dac-omitinib covalent binding and inhibition of multiple ErbB family receptors (EGFR, HER2 and HER4). People evaluate these drugs as ifrst-line treatment of signiifcance, and acquired drug resistance situation signiifcance on the ifrst generation EGFR-TKIs. Afatinib is the ifrst ErbB family approved blocking agent, used to treat with EGFR activatingmutations in patients with non small cell lung cancer; dacomitinib are in the later stages of clinicaldevel-opment. EGFR inhibitors speciifcally targeting T790M resistance mutations (AZD9291, CO-1686, HM61713) are in the early stages of development. As discussed in this paper, the scope of the EGFR-TKIs kinase to target different, EGFR receptor bind-ing was reversible and drug interaction potential is also different. For clinicians, these differences of the multi drug treatment of patients with non-small cell lung cancer with meaning, from the innovative anticancer drug combination therapy strategy point of view, these differences are also of great signiifcance.
