Mechanisms of resistance to EGFR tyrosine kinase inhibitors.
10.1016/j.apsb.2015.07.001
- Author:
Lihua HUANG
1
;
Liwu FU
1
Author Information
1. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China.
- Publication Type:Journal Article
- Keywords:
ABC, ATP binding cassette;
ABCB1, ATP binding cassette, sub-family B, member 1;
ABCC1, ATP binding cassette, sub-family C, member 1;
ABCC10, ATP binding cassette, sub-family C, member 10;
ABCG2, ATP binding cassette, sub-family G, member 2;
AKT, protein kinase B;
ALK, anaplastic lymphoma kinase;
AXL, Anexelekto;
BCL-2, B-cell CLL/lymphoma-2;
BCL2L11/BIM, BCL2-like 11;
BH3, BCL2-homology domain 3;
BRAF, v-RAF murine sarcoma viral oncogene homolog B1;
CML, chronic myelogenous leukemia;
CRKL, Crk-like protein;
EGFR;
EGFR, epidermal growth factor receptor;
EGFR-TKIs, epidermal growth factor receptor tyrosine kinase inhibitors;
EGFRvIII, EGFR variant III;
EML4, echinoderm microtubule-associated protein-like 4;
EMT, epithelial mesenchymal transition;
ERK1/2, extracellular signal-regulated kinases;
FGFRs, fibroblast growth factor receptors;
FGFs, fibroblast growth factors;
GAS6, growth-arrest-specific protein 6;
HER, human epidermal receptor;
HGF, hepatocyte growth factor;
IGF, insulin growth factor;
IGF-1R, IGF-1 receptor;
IGFBPs, IGF-binding proteins;
IL, interleukin;
IL-6R, IL-6 receptor;
JAK, janus kinase;
MAPK, mitogen-activated protein kinase;
MEK, mitogen-activated protein kinase;
Mechanisms;
NSCLC, non-small cell lung cancer;
PDGFRs, platelet-derived growth factor receptors;
PDGFs, platelet-derived growth factors;
PI3K, phosphatidylinositol-3-kinase;
PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase,catalytic subunit alpha;
PTEN, phosphatase and tensin homolog;
RAF, rapidly accelerated fibrosarcoma;
RAS, rat sarcoma;
RTK, tyrosine kinase receptor;
Resistance;
SF, scatter factor;
SOCS3, suppressor of cytokine signaling 3;
STAT, signal transducers and activators of transcription;
TKIs;
TKIs, tyrosine kinase inhibitors;
TKs, tyrosine kinases;
VEGF, vascular endothelial growth factor;
VEGFR, vascular endothelial growth factor receptor
- From:
Acta Pharmaceutica Sinica B
2015;5(5):390-401
- CountryChina
- Language:English
-
Abstract:
Since the discovery that non-small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation (T790M), activation of alternative pathways (c-Met, HGF, AXL), aberrance of the downstream pathways (K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette (ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies.
