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T790M 突变导致的酪氨酸激酶抑制剂耐药性

[TKI Resistance for T790M Mutation].

作者信息

Wang Hong, Guo Rui, Zhang Liyu

机构信息

Deputy Director of Lung Tumor Department, 307 Hospital, Beijing 100071, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2015 Apr;18(4):245-50. doi: 10.3779/j.issn.1009-3419.2015.04.10.

Abstract

Epidermal growth factor receptor (EGFR) the development of orally activesmall 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 benefit. The first generation of reversible ATP-competitive EGFR-TKIs, gefitinib and erlotinib as first-line, second-line or has the effect of maintenance therapy. Although the initial effect of these drugs have, but most patients will produce 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 first-line treatment of significance, and acquired drug resistance situation significance on the first generation EGFR-TKIs. Afatinib is the first ErbB family approved blocking agent, used to treat with EGFR activating mutations in patients with non small cell lung cancer; dacomitinib are in the later stages of clinical development. EGFR inhibitors specifically 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 binding 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 significance.

摘要

表皮生长因子受体(EGFR)口服活性小分子抑制剂的研发为非小细胞肺癌(NSCLC)提供了新的治疗方案。EGFR基因突变的患者对EGFR酪氨酸激酶抑制剂(EGFR-TKIs)治疗敏感,从而获得大量临床益处。第一代可逆性ATP竞争性EGFR-TKIs,吉非替尼和厄洛替尼可作为一线、二线或维持治疗用药。尽管这些药物初期有效果,但大多数患者会产生耐药性。一年内,50%-60%的患者出现与T790M看家基因相关的突变。近期不可逆性EGFR-TKIs的背景:阿法替尼和达可替尼可共价结合并抑制多个ErbB家族受体(EGFR、HER2和HER4)。人们评估这些药物作为一线治疗的意义,以及对第一代EGFR-TKIs获得性耐药情况的意义。阿法替尼是首个获批的ErbB家族阻断剂,用于治疗具有EGFR激活突变的非小细胞肺癌患者;达可替尼正处于临床开发后期。特异性靶向T790M耐药突变的EGFR抑制剂(AZD9291、CO-1686、HM61713)正处于开发早期。如本文所讨论的,EGFR-TKIs激酶靶向范围不同,与EGFR受体的结合是可逆的,药物相互作用潜力也不同。对于临床医生而言,这些差异对非小细胞肺癌患者的多药治疗有意义,从创新抗癌药物联合治疗策略的角度来看,这些差异也具有重要意义。

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[TKI Resistance for T790M Mutation].T790M 突变导致的酪氨酸激酶抑制剂耐药性
Zhongguo Fei Ai Za Zhi. 2015 Apr;18(4):245-50. doi: 10.3779/j.issn.1009-3419.2015.04.10.

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