目前最全EGFR耐药机制总结

http://www.ncbi.nlm.nih.gov/pubmed/26579470Acta Pharm Sin B.
2015 Sep;5(5):390-401. doi: 10.1016/j.apsb.2015.07.001. Epub  2015 Jul 26.
Mechanisms of resistance to EGFR tyrosine kinase inhibitors.
1、EGFR突变信号通路

                               
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2、EGFR二次突变，主要是T790M,其次是 L747S, D761Y and T854A
3、旁通信号bypass
3.1  HER 其他家族成员的异常
3.2 CMT扩增
3.3 HGF过表达
3.4 IGFR异常
3.5 异常血管生长通路
    3.5.1 VEGFs 及其受体
   3.5.2  FGFs 及其受体
  3.5.3.  PDGFRs及其受体
3.6. EGFRvIII
3.7. AXL过表达
3.8. IL-6过分泌
3.9. Amplification of Crk-like protein (CRKL扩增)
3.10. Overexpression and activation of integrin beta1-整合素β1的过表达和激活
4、异常下游信号
4.1. K-RAS 突变
4.2.  PTEN丢失
4.3. BRAF突变
4.4.  PIK3CA突变
4.5. NF1异常表达
5. BIM损伤
6、组织类型的变化
6.1. EMT
6.2小细胞肺癌转换
7. ATP binding cassette (ABC) effusion
8. EML4-ALK融合基因和二次突变
9。治疗策略：联合治疗

Resistant mechanism 耐药机制	Strategy 治疗策略	Clinical research 临床研究	Ref. 参考文献
EGFRmutation
T790M	EGFR-TKIs combined/+antibodies	Afatinib+cexitumab	80
	T790M-specific inhibitors	CO-1686/AZD9291	81, 82
	c-Met inhibitors+PI3K inhibitors	GDC0973+GDC0941	83
	HSP90 inhibitors	Luteolin/ganetespib	11, 84

	EGFR-TKIs+MEK inhibitors	Afatinib+ARQ 197	85
	Glycolysis inhibition+EGFR-TKIs	Afatinib+AUY922	86
Bypass pathway
HER family abnormality	HER inhibitors+EGFR-TKIs	Afatinib/dacomitinib	18, 87
c-Met amplification	EGFR-TKIs+c-Met inhibitors	Erlotinib+crizotinib	88
Dacomitinib+crizotinib
HGF overexpression	EGFR-TKIs+PI3K inhibitors	Gefitinib+PI-103	89
	Triple inhibition of EGFR/Met/VEGF	–	90
IGFR abnormality	IGFR inhibitors+EGFR-TKIs	AG1024+gefitinib	–

EGFRvIII	EGFRvIII antibodies	–	–
VEGF/VEGFR abnormality	EGFR-TKIs+VEGF inhibitors	ZD6474	91
	MEK inhibitors+VEGF inhibitors	ZD6474+PD0325901	30
PDGF/PDGFR abnormality	EGFR-TKIs+PDGF inhibitors	–	–
FGF/FGFR abnormality	EGFR-TKIs+FGF inhibitors	–	–
IL-6 abnormality	IL-6 antibodies	Siltuximab	92
AXL abnormality	AXL inhibitors	NPS-1034	93
CRKL amplification	Unknown	Unknown	–
Integrin beta1 overexpression	Unknown	Unknown	–
Downstream pathway
K-RAS mutations	PI3K inhibitors+MEK inhibitors	GDC-0941+AZD6244	94
BRAF mutations	BRAF inhibitors+MEK inhibitors	Dabrafenib+trametinib	95
Loss of PTEN	mTOR inhibitors/AKT

inhibitors	–	–
PIK3CA mutation	EGFR-TKIs+PI3K inhibitors	Gefitinib+BKM120	96
Low expression of NF1	Unknown	Unknown	–
Apoptosis pathway
BIM BH3 deletion	EGFR-TKIs+PP2A activator	Erlotinib+FTY720 gefitinib+FTY720	62
Histologic transformation
EMT	EGFR-TKIs+MEK1/2 inhibitors	–	–

SCLC transformation	Platinum+VP16/EGFR-TKIs	–	–
ABC effusion	EGFR-TKIs+HER-2 inhibitors	GW583340/GW2974	73
Unknown mechanism	EGFR-TKIs combined	Afatinib+cexitumab	80
EGFR-TKIs+glycolysis inhibitors	Erlotinib+AUY922

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感谢楼主分享

完全看不懂

这个真是太全了，好好研究一下。
看了一下作者，是中山大学的黄丽华等，但没找到中文的文章。

感谢楼主提供详细信息。

多谢楼主的用心整理收集。

感谢楼主分享

总结得非常好，这么多突变检测起来非常困难。按照这样精准治疗看来非常困难。还是要设法找到更为有效之法。

这么全，反而看糊涂了

功力不够，希望有进一步的剖析说明，谢谢！