AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers(m CRCs) addicted to epidermal growth factor receptor(EGFR) signalling.METHODS: The present study summarizes the potential value of prog...AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers(m CRCs) addicted to epidermal growth factor receptor(EGFR) signalling.METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting m CRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of Pub Med, Medline and Web of Science to identify eligible papers until March 21 st, 2016 using these following terms: ‘‘colorectal cancer'', "predictive biomarkers' ', "anti-EGFR therapy", "KRAS", "NRAS'', "PIK3CA", "TP53", "PTEN", ‘‘EGFR", "MET", "HER2", "epiregulin", "amphiregulin", "prognostic biomarkers", "BRAF", "miR NA" and "antibody-dependent cell-mediated cytotoxicity(ADCC) activity". Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and exclusion. RESULTS: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mC RCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mR NA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3 CA. The prognostic value of selected micro RNAs level and ADCC activity is under investigation, while the prognostic impact of BRAF status remains controversial.CONCLUSION: This review focuses on the personalized treatment of m CRC and discusses the potential of new prognostic and predictive biomarkers in selecting patients treated with anti-EGFR therapy.展开更多
文摘AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers(m CRCs) addicted to epidermal growth factor receptor(EGFR) signalling.METHODS: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting m CRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of Pub Med, Medline and Web of Science to identify eligible papers until March 21 st, 2016 using these following terms: ‘‘colorectal cancer'', "predictive biomarkers' ', "anti-EGFR therapy", "KRAS", "NRAS'', "PIK3CA", "TP53", "PTEN", ‘‘EGFR", "MET", "HER2", "epiregulin", "amphiregulin", "prognostic biomarkers", "BRAF", "miR NA" and "antibody-dependent cell-mediated cytotoxicity(ADCC) activity". Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and exclusion. RESULTS: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mC RCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mR NA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3 CA. The prognostic value of selected micro RNAs level and ADCC activity is under investigation, while the prognostic impact of BRAF status remains controversial.CONCLUSION: This review focuses on the personalized treatment of m CRC and discusses the potential of new prognostic and predictive biomarkers in selecting patients treated with anti-EGFR therapy.
