title: Expression of pEGFR and pAKT as response-predictive biomarkers for RAS wild-type patients to anti-EGFR monoclonal antibodies in metastatic colorectal cancers.
abstract: 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.
authors.affiliation: 1] Université de Lorraine, Faculté de Pharmacie, 54001 Nancy, France [2] CNRS UMR 7039 CRAN, 54506 Vandoeuvre les Nancy, France [3] Institut de Cancérologie de Lorraine, Service de Biopathologie, 54519 Vandoeuvre les Nancy, France.
authors.forename: A
authors.initials: A
authors.lastname: Harlé
authors.affiliation: Institut de Cancérologie de Lorraine, Cellule Data Biostatistique, 54519 Vandoeuvre les Nancy, France.
authors.forename: J
authors.initials: J
authors.lastname: Salleron
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR)-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Perkins
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR)-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Pilati
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR)-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Blons
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR)-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Université Paris Descartes, 45 rue des Saints Pères, 75006 Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Laurent-Puig
authors.affiliation: 1] Université de Lorraine, Faculté de Pharmacie, 54001 Nancy, France [2] CNRS UMR 7039 CRAN, 54506 Vandoeuvre les Nancy, France [3] Institut de Cancérologie de Lorraine, Service de Biopathologie, 54519 Vandoeuvre les Nancy, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Merlin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D048369:MAP Kinase Kinase 1; D018631:ras Proteins