癌症研究
生物
蛋白激酶B
表皮生长因子受体
酪氨酸激酶
受体酪氨酸激酶
蛋白激酶结构域
信号转导
埃罗替尼
MAPK/ERK通路
PI3K/AKT/mTOR通路
激酶
癌症
细胞生物学
遗传学
突变体
基因
作者
Qian Liu,Shengnan Yu,Wei Zhao,Shuang Qin,Qian Chu,Kongming Wu
标识
DOI:10.1186/s12943-018-0793-1
摘要
Tyrosine kinase inhibitors (TKIs)-treatments bring significant benefit for patients harboring epidermal growth factor receptor (EGFR) mutations, especially for those with lung cancer. Unfortunately, the majority of these patients ultimately develop to the acquired resistance after a period of treatment. Two central mechanisms are involved in the resistant process: EGFR secondary mutations and bypass signaling activations. In an EGFR-dependent manner, acquired mutations, such as T790 M, interferes the interaction between TKIs and the kinase domain of EGFR. While in an EGFR-independent manner, dysregulation of other receptor tyrosine kinases (RTKs) or abnormal activation of downstream compounds both have compensatory functions against the inhibition of EGFR through triggering phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling axes. Nowadays, many clinical trials aiming to overcome and prevent TKIs resistance in various cancers are ongoing or completed. EGFR-TKIs in accompany with the targeted agents for resistance-related factors afford a promising first-line strategy to further clinical application.
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