Additional value of EGFR downstream signaling phosphoprotein expression to KRAS status for response to anti-EGFR antibodies in colorectal cancer.
作者： Geraldine Perkins , Astrid Lièvre , Carole Ramacci , Tchao Méatchi , Aurélien de Reynies
DOI: 10.1002/IJC.25152
关键词: Cancer 、 Epidermal growth factor receptor 、 Panitumumab 、 Growth factor receptor 、 KRAS 、 Cetuximab 、 Immunology 、 Medicine 、 Cancer research 、 Colorectal cancer 、 Predictive marker
摘要: KRAS mutations are a strong predictive marker of resistance to anti-epidermal growth factor receptor (EGFR) antibodies in advanced colorectal cancer (CRC) but only subset wild-type (WT) patients responders, suggesting the existence additional markers this treatment. The activation EGFR downstream signaling pathways may be one these ones. In series 42 with CRC treated cetuximab/panitumumab, for whom status was previously determined, we retrospectively analyzed intratumor expression phosphoproteins RAS/MAPK and PI3K/AKT (pERK1/2, pMEK1, pAKT, pP70S6K pGSK3beta) using Bio-Plex phosphoprotein array. Association tumor response, progression-free survival (PFS) overall (OS) assessed. all higher mutated tumors than WT tumors. lower responders nonresponder patients. univariate analysis, high pMEK1 or had shorter PFS those low expression. Patients also OS. multivariate expression, independently status, as OS Therefore, Our results suggest importance addition define subgroup who will not benefit from anti-EGFR therapy.
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