PMID- 24050852
OWN - NLM
STAT- MEDLINE
DCOM- 20140912
LR  - 20181202
IS  - 1938-0674 (Electronic)
IS  - 1533-0028 (Linking)
VI  - 12
IP  - 4
DP  - 2013 Dec
TI  - The prognostic role of ephrin A2 and endothelial growth factor receptor pathway 
      mediators in patients with advanced colorectal cancer treated with cetuximab.
PG  - 267-274.e2
LID - S1533-0028(13)00074-1 [pii]
LID - 10.1016/j.clcc.2013.07.001 [doi]
AB  - BACKGROUND: Patients with colorectal cancer (CRC) with wild-type KRAS mutations 
      are often treated with the endothelial growth factor receptor (EGFR) monoclonal 
      antibody cetuximab. Despite the presence of a specific molecular target, most 
      patients still do not derive benefit from this biological treatment. Our study 
      explores the role of ephrin A2 (EphA2) receptor expression and of EGFR pathway 
      mediators as predictors of cetuximab benefit. PATIENTS AND METHODS: 
      Formalin-fixed paraffin-embedded (FFPE) tumor biopsy samples from 226 
      cetuximab-treated patients with CRC were studied for mRNA expression of insulin 
      growth factor binding protein 2 (IGFBP2), insulin growth factor receptor 1 
      (IGF1R), cMET, EphA2, human epidermal growth factor receptor 2 (HER2), HER3, and 
      HER4 by means of TaqMan reverse-transcribed polymerase chain reaction (RT-PCR). 
      RESULTS: Of the 226 patients evaluable for exploratory analysis, 222 had complete 
      data from follow-up visits. The univariate analysis revealed the following 
      significant adverse prognostic factors for risk of death: high EphA2 mRNA levels 
      (hazard ratio [HR], 1.61; P = .015), high HER2 mRNA levels (HR, 1.51; P = .045), 
      and high IGF1R mRNA levels (HR, 1.56; P = .021). Low EphA2 tumor expression was 
      significantly associated with objective response to cetuximab therapy. In 
      multivariate analysis of a broad biomarker panel, factors with independent 
      prognostic value included EphA2 mRNA levels (HR, 1.67; P = .029), high 
      amphiregulin (AREG) mRNA levels in KRAS wild-type tumors (HR, 0.17; P < .0001), 
      and high epiregulin (EREG) mRNA levels (HR, 0.38; P = .006). CONCLUSION: High 
      EphA2 receptor expression in CRC was associated with a worse outcome in patients 
      treated with cetuximab-based therapy. Prospective validation in treated and 
      control patients is required to dissect the predictive from prognostic role in 
      advanced CRC.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Strimpakos, Alexios
AU  - Strimpakos A
AD  - Oncology Unit, Third Department of Medicine, "Sotiria" General Hospital, Athens 
      School of Medicine, Athens, Greece. Electronic address: alexstrimp@med.uoa.gr.
FAU - Pentheroudakis, George
AU  - Pentheroudakis G
FAU - Kotoula, Vassiliki
AU  - Kotoula V
FAU - De Roock, Wendy
AU  - De Roock W
FAU - Kouvatseas, George
AU  - Kouvatseas G
FAU - Papakostas, Pavlos
AU  - Papakostas P
FAU - Makatsoris, Thomas
AU  - Makatsoris T
FAU - Papamichael, Demetris
AU  - Papamichael D
FAU - Andreadou, Anna
AU  - Andreadou A
FAU - Sgouros, Joseph
AU  - Sgouros J
FAU - Zizi-Sermpetzoglou, Adamantia
AU  - Zizi-Sermpetzoglou A
FAU - Kominea, Athina
AU  - Kominea A
FAU - Televantou, Despina
AU  - Televantou D
FAU - Razis, Evangelia
AU  - Razis E
FAU - Galani, Eleni
AU  - Galani E
FAU - Pectasides, Dimitrios
AU  - Pectasides D
FAU - Tejpar, Sabine
AU  - Tejpar S
FAU - Syrigos, Konstantinos
AU  - Syrigos K
FAU - Fountzilas, George
AU  - Fountzilas G
LA  - eng
PT  - Journal Article
DEP - 20130917
PL  - United States
TA  - Clin Colorectal Cancer
JT  - Clinical colorectal cancer
JID - 101120693
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Ephrin-A2)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Adenocarcinoma/drug therapy/*metabolism/mortality
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
MH  - Antineoplastic Agents/therapeutic use
MH  - Biomarkers, Tumor/*analysis
MH  - Cetuximab
MH  - Colorectal Neoplasms/drug therapy/*metabolism/mortality
MH  - Ephrin-A2/*metabolism
MH  - ErbB Receptors/metabolism
MH  - Female
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*physiology
EDAT- 2013/09/21 06:00
MHDA- 2014/09/13 06:00
CRDT- 2013/09/21 06:00
PHST- 2013/02/13 00:00 [received]
PHST- 2013/07/15 00:00 [accepted]
PHST- 2013/09/21 06:00 [entrez]
PHST- 2013/09/21 06:00 [pubmed]
PHST- 2014/09/13 06:00 [medline]
AID - S1533-0028(13)00074-1 [pii]
AID - 10.1016/j.clcc.2013.07.001 [doi]
PST - ppublish
SO  - Clin Colorectal Cancer. 2013 Dec;12(4):267-274.e2. doi: 
      10.1016/j.clcc.2013.07.001. Epub 2013 Sep 17.