PMID- 26667342
OWN - NLM
STAT- MEDLINE
DCOM- 20160505
LR  - 20220321
IS  - 0065-2598 (Print)
IS  - 0065-2598 (Linking)
VI  - 893
DP  - 2016
TI  - Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors and Therapeutic 
      Approaches: An Update.
PG  - 137-153
LID - 10.1007/978-3-319-24223-1_7 [doi]
AB  - Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors 
      (TKIs) in non small cell lung cancer (NSCLC) is mediated by two major mechanisms 
      namely secondary mutation T790M in EGFR and cMET amplification. Other molecular 
      mediators which contribute towards TKI resistance include the activation of 
      compensatory growth signaling, epithelial mesenchymal transition and microRNAs 
      regulating EGFR and cMET levels. In this chapter, we have included the major 
      mechanisms which contribute towards EGFR TKI resistance in NSCLC. Several 
      therapeutic approaches to overcome TKI resistance are also presented which 
      include second and third generation EGFR TKI inhibitors and cMET inhibitors. 
      Further, the rationale to utilize the combination therapies to simultaneously 
      target EGFR and other major oncogene addictive pathway such as ERBB2 and AXL 
      kinase is outlined. Another promising approach to overcome TKI resistance is to 
      potentiate EGFR protein for degradation. These studies will best be utilized when 
      we can identify the oncogene addictions in an individual patient and tailor the 
      therapy/therapies accordingly for the maximum benefits.
FAU - Ahsan, Aarif
AU  - Ahsan A
AD  - Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 48109, 
      USA. aarif.ahsan@pfizer.com.
AD  - Bioconjugate Drug Discovery, Oncology Research Unit, Pfizer Inc., 401 N. 
      Middletown Rd., Pearl River, NY, 10965, USA. aarif.ahsan@pfizer.com.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Adv Exp Med Biol
JT  - Advances in experimental medicine and biology
JID - 0121103
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Drug Resistance, Neoplasm
MH  - Epigenesis, Genetic
MH  - Epithelial-Mesenchymal Transition
MH  - ErbB Receptors/*antagonists & inhibitors/genetics
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Mutation
MH  - Protein Kinase Inhibitors/pharmacology/*therapeutic use
MH  - Proto-Oncogene Proteins c-met/antagonists & inhibitors
OTO - NOTNLM
OT  - EGFR
OT  - Erlotinib
OT  - Non small cell lung cancer
OT  - TKI resistance
OT  - cMET
EDAT- 2015/12/17 06:00
MHDA- 2016/05/06 06:00
CRDT- 2015/12/16 06:00
PHST- 2015/12/16 06:00 [entrez]
PHST- 2015/12/17 06:00 [pubmed]
PHST- 2016/05/06 06:00 [medline]
AID - 10.1007/978-3-319-24223-1_7 [doi]
PST - ppublish
SO  - Adv Exp Med Biol. 2016;893:137-153. doi: 10.1007/978-3-319-24223-1_7.