Molecular markers associated with anti-EGFR monoclonal antibody in treatment selection for advanced colorectal cancer / 肿瘤

ABSTRACT

Personalized targeted therapy in addition to standard chemotherapy has become a hot topic in the treatment of metastatic colorectal cancer (mCRC). KRAS gene mutation has been considered as a predictor for poor response to anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR) therapy in patients with mCRC. The percentage of KRAS mutation is 35%-45% in patients with mCRC, and these patients have poor response to anti-EGFR; while only 50% of patients with wild-type KRAS respond to anti-EGFR, which suggests that the activation and variation of other molecules in the downstream of EGFR signaling pathway can influence the therapeutic effects. The two major EGFR-dependent signaling pathways - RAS-RAF-MAPK and PI3K-PTEN-AKT may be involved in poor response to anti-EGFR in the treatment of mCRC. In addition, the increased EGFR gene copy number (GCN) is associated with the efficacy of anti-EGFR therapy, but not associated with the expression level of EGFR protein which has no correlation with the efficacy of anti-EGFR therapy. Additional detection of mutations in BRAF and PIK3CA genes as well as deletion of PTEN gene in wild-type KRAS patients with mCRC may be helpful in further selection of patients with anti-EGFR resistance. This paper reviews recent progress on molecular markers associated with treatment outcome and prognosis predictions in the treatment of mCRC, in order to guide individualized molecular targeted therapy for mCRC. Copyright© 2011 by TUMOR.