PMID- 26171935
OWN - NLM
STAT- MEDLINE
DCOM- 20151028
LR  - 20181202
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 113
IP  - 4
DP  - 2015 Aug 11
TI  - Expression of pEGFR and pAKT as response-predictive biomarkers for RAS wild-type 
      patients to anti-EGFR monoclonal antibodies in metastatic colorectal cancers.
PG  - 680-5
LID - 10.1038/bjc.2015.250 [doi]
AB  - BACKGROUND: RAS wild-type (RASw/t) tumours have been associated with better 
      outcomes in patients with metastatic colorectal cancer (mCRC) treated with 
      anti-EGFR monoclonal antibodies (mAb). We investigated the expression of EGFR 
      downstream proteins under their active phosphorylated forms as potential markers 
      in response to these patients. METHODS: One-hundred tumour samples were collected 
      from patients with mCRC refractory to FOLFOX and/or FOLFIRI and treated by a 
      combination of chemotherapy with anti-EGFR mAb. The outcomes were measured on 
      response evaluation criteria in solid tumour (RECIST), progression-free survival 
      (PFS) and overall survival (OS). All samples were assessed for RAS and BRAF 
      mutations, and the key phosphorylated proteins of EGFR downstream signalling were 
      quantitatively analysed using the BioPlex Protein array. RESULTS: Among the 60 
      RASw/t patients, 45.0% achieved a complete or partial response when treated with 
      anti-EGFR mAb. Expression of pAKT, pERK1/2 and pMEK1 was significantly lower in 
      RASw/t patients (P=0.0246; P=0.004; P=0.0110, respectively). The response rate 
      was significantly higher for RASw/t patients who express pEGFR and pAKT 
      (P=0.0258; P=0.0277, respectively). CONCLUSIONS: Overexpression of pEGFR and pAKT 
      may predict the response rate in RASw/t patients treated with anti-EGFR mAb. On 
      the basis of our results, we hypothesise that the association of anti-EGFR mAb 
      and anti-AKT therapies could be of interest.
FAU - Harle, A
AU  - Harle A
AD  - 1] Universite de Lorraine, Faculte de Pharmacie, 54001 Nancy, France [2] CNRS UMR 
      7039 CRAN, 54506 Vandoeuvre les Nancy, France [3] Institut de Cancerologie de 
      Lorraine, Service de Biopathologie, 54519 Vandoeuvre les Nancy, France.
FAU - Salleron, J
AU  - Salleron J
AD  - Institut de Cancerologie de Lorraine, Cellule Data Biostatistique, 54519 
      Vandoeuvre les Nancy, France.
FAU - Perkins, G
AU  - Perkins G
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM), Unite Mixte 
      de Recherche (UMR)-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic 
      Optimization, Universite Paris Descartes, 45 rue des Saints Peres, 75006 Paris, 
      France.
FAU - Pilati, C
AU  - Pilati C
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM), Unite Mixte 
      de Recherche (UMR)-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic 
      Optimization, Universite Paris Descartes, 45 rue des Saints Peres, 75006 Paris, 
      France.
FAU - Blons, H
AU  - Blons H
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM), Unite Mixte 
      de Recherche (UMR)-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic 
      Optimization, Universite Paris Descartes, 45 rue des Saints Peres, 75006 Paris, 
      France.
FAU - Laurent-Puig, P
AU  - Laurent-Puig P
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM), Unite Mixte 
      de Recherche (UMR)-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic 
      Optimization, Universite Paris Descartes, 45 rue des Saints Peres, 75006 Paris, 
      France.
FAU - Merlin, J L
AU  - Merlin JL
AD  - 1] Universite de Lorraine, Faculte de Pharmacie, 54001 Nancy, France [2] CNRS UMR 
      7039 CRAN, 54506 Vandoeuvre les Nancy, France [3] Institut de Cancerologie de 
      Lorraine, Service de Biopathologie, 54519 Vandoeuvre les Nancy, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150714
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Biomarkers, Tumor/*genetics
MH  - Colorectal Neoplasms/*drug therapy/*genetics
MH  - Disease-Free Survival
MH  - ErbB Receptors/*genetics
MH  - Female
MH  - Humans
MH  - MAP Kinase Kinase 1/genetics
MH  - MAP Kinase Signaling System/drug effects/genetics
MH  - Male
MH  - Middle Aged
MH  - Phosphorylation/drug effects/genetics
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Proto-Oncogene Proteins c-akt/*genetics
MH  - Signal Transduction/drug effects/genetics
MH  - Young Adult
MH  - ras Proteins/*genetics
PMC - PMC4647679
EDAT- 2015/07/15 06:00
MHDA- 2015/10/29 06:00
PMCR- 2016/08/11
CRDT- 2015/07/15 06:00
PHST- 2015/01/13 00:00 [received]
PHST- 2015/04/03 00:00 [revised]
PHST- 2015/06/16 00:00 [accepted]
PHST- 2015/07/15 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2015/10/29 06:00 [medline]
PHST- 2016/08/11 00:00 [pmc-release]
AID - bjc2015250 [pii]
AID - 10.1038/bjc.2015.250 [doi]
PST - ppublish
SO  - Br J Cancer. 2015 Aug 11;113(4):680-5. doi: 10.1038/bjc.2015.250. Epub 2015 Jul 
      14.