Expression of pEGFR and pAKT as response-predictive biomarkers for RAS wild-type patients to anti-EGFR monoclonal antibodies in metastatic colorectal cancers.
Fiche publication
Date publication
août 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HARLE Alexandre, Pr MERLIN Jean-Louis
Tous les auteurs :
Harle A, Salleron J, Perkins G, Pilati C, Blons H, Laurent-Puig P, Merlin JL
Lien Pubmed
Résumé
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.
Référence
Br J Cancer. 2015 Aug 11;113(4):680-5