PMID- 30473379
OWN - NLM
STAT- MEDLINE
DCOM- 20190610
LR  - 20231005
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 39
DP  - 2019 Jan
TI  - Integrin-linked kinase (ILK) and src homology 2 domain-containing phosphatase 2 
      (SHP2): Novel targets in EGFR-mutation positive non-small cell lung cancer 
      (NSCLC).
PG  - 207-214
LID - S2352-3964(18)30541-3 [pii]
LID - 10.1016/j.ebiom.2018.11.036 [doi]
AB  - BACKGROUND: The activation of multiple signaling pathways jeopardizes the 
      clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutation 
      positive non-small cell lung cancer (NSCLC). Integrin-linked kinase (ILK) 
      regulates the interactions between tumor cells and extracellular environment to 
      activate signaling pathways and promote cell proliferation, migration, and 
      epithelial-mesenchymal transition. Src homology 2 domain-containing phosphatase 2 
      (SHP2) is essential for receptor tyrosine kinase signaling and mitogen-activated 
      protein kinase (MAPK) pathway activation. METHODS: We analyzed tumor ILK, 
      beta-receptor subunit glycoprotein 130 (gp130), SHP2, and stromal hepatocyte growth 
      factor (HGF) and interleukin-6 (IL-6) mRNA expression in baseline tumor specimens 
      of advanced EGFR-mutation positive NSCLC patients treated with EGFR TKIs. 
      RESULTS: ILK, when highly expressed, was an independent poor prognostic factor 
      for the progression-free survival of the patients, both in the univariate (hazard 
      ratio [HR for disease progression, 2.49; 95% CI, 1.37-4.52; P = .0020]) and in 
      the multivariate (HR 3.74; 95% CI, 1.33-10.56; P = .0126) Cox regression model. 
      Patients with high SHP2 expression had an almost 13-month shorter 
      progression-free survival (P = .0094) and an 18-month shorter overall survival 
      (P = .0182) in comparison to those with low SHP2 mRNA expression. INTERPRETATION: 
      The levels of ILK and SHP2 could be predictive for upfront combinatory therapy of 
      EGFR TKIs plus SHP2 or ILK inhibitors. FUND: A grant from La Caixa Foundation, an 
      Instituto de Salud Carlos III grant (RESPONSE, PIE16/00011), an Instituto de 
      Salud Carlos III grant (PI14/01678), a Marie Sklodowska-Curie Innovative Training 
      Networks European Grant (ELBA No 765492) and a Spanish Association Against Cancer 
      (AECC) grant (PROYE18012ROSE).
CI  - Copyright (c) 2018 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Karachaliou, Niki
AU  - Karachaliou N
AD  - Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, QuironSalud 
      Group, Barcelona, Spain; Coyote Research Group, Pangaea Oncology, Laboratory of 
      Molecular Biology, Quiron-Dexeus University Institute, Barcelona, Spain. 
      Electronic address: dr.nikikarachaliou@gmail.com.
FAU - Cardona, Andres Felipe
AU  - Cardona AF
AD  - Clinica del Country, Bogota, Colombia.
FAU - Bracht, Jillian Wilhelmina Paulina
AU  - Bracht JWP
AD  - Coyote Research Group, Pangaea Oncology, Laboratory of Molecular Biology, 
      Quiron-Dexeus University Institute, Barcelona, Spain.
FAU - Aldeguer, Erika
AU  - Aldeguer E
AD  - Coyote Research Group, Pangaea Oncology, Laboratory of Molecular Biology, 
      Quiron-Dexeus University Institute, Barcelona, Spain.
FAU - Drozdowskyj, Ana
AU  - Drozdowskyj A
AD  - Pivotal, Madrid, Spain.
FAU - Fernandez-Bruno, Manuel
AU  - Fernandez-Bruno M
AD  - Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, QuironSalud 
      Group, Barcelona, Spain.
FAU - Chaib, Imane
AU  - Chaib I
AD  - Institut d'Investigacio en Ciencies Germans Trias i Pujol, Badalona, Spain.
FAU - Berenguer, Jordi
AU  - Berenguer J
AD  - Coyote Research Group, Pangaea Oncology, Laboratory of Molecular Biology, 
      Quiron-Dexeus University Institute, Barcelona, Spain.
FAU - Santarpia, Mariacarmela
AU  - Santarpia M
AD  - Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of 
      Messina, Messina, Italy.
FAU - Ito, Masaoki
AU  - Ito M
AD  - Coyote Research Group, Pangaea Oncology, Laboratory of Molecular Biology, 
      Quiron-Dexeus University Institute, Barcelona, Spain.
FAU - Codony-Servat, Jordi
AU  - Codony-Servat J
AD  - Coyote Research Group, Pangaea Oncology, Laboratory of Molecular Biology, 
      Quiron-Dexeus University Institute, Barcelona, Spain.
FAU - Rosell, Rafael
AU  - Rosell R
AD  - Coyote Research Group, Pangaea Oncology, Laboratory of Molecular Biology, 
      Quiron-Dexeus University Institute, Barcelona, Spain; Institut d'Investigacio en 
      Ciencies Germans Trias i Pujol, Badalona, Spain; Institut Catala d'Oncologia, 
      Hospital Germans Trias i Pujol, Badalona, Spain. Electronic address: 
      rrosell@iconcologia.net.
LA  - eng
PT  - Journal Article
DEP - 20181122
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - 0 (HGF protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.1.- (integrin-linked kinase)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.1.3.48 (PTPN11 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
SB  - IM
CIN - EBioMedicine. 2019 Jan;39:5-6. PMID: 30553753
MH  - Aged
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Hepatocyte Growth Factor/genetics
MH  - Humans
MH  - Interleukin-6/genetics
MH  - Lung Neoplasms/*genetics
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Mutation
MH  - Progression-Free Survival
MH  - Protein Kinase Inhibitors/pharmacology/therapeutic use
MH  - Protein Serine-Threonine Kinases/*genetics
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11/*genetics
MH  - Regression Analysis
MH  - *Up-Regulation
PMC - PMC6354556
OTO - NOTNLM
OT  - EGFR mutations
OT  - Integrin-linked kinase
OT  - NSCLC
OT  - Signaling pathways
OT  - Src homology 2 domain-containing phosphatase 2
EDAT- 2018/11/27 06:00
MHDA- 2019/06/14 06:00
PMCR- 2018/11/22
CRDT- 2018/11/27 06:00
PHST- 2018/11/05 00:00 [received]
PHST- 2018/11/16 00:00 [revised]
PHST- 2018/11/16 00:00 [accepted]
PHST- 2018/11/27 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/11/27 06:00 [entrez]
PHST- 2018/11/22 00:00 [pmc-release]
AID - S2352-3964(18)30541-3 [pii]
AID - 10.1016/j.ebiom.2018.11.036 [doi]
PST - ppublish
SO  - EBioMedicine. 2019 Jan;39:207-214. doi: 10.1016/j.ebiom.2018.11.036. Epub 2018 
      Nov 22.