TITLE:
Molecular Markers for the Prediction of Anti-EGFR Monoclonal Antibody Treatment Efficacy in Metastatic Colorectal Cancer
AUTHORS:
Cheng-Bo Han, Jie-Tao Ma, Fan Li, Hua-Wei Zou
KEYWORDS:
Molecular Marker, Epidermal Growth Factor Receptor, Kras, EGFR Monoclonal Antibody, Metastatic Colorectal Cancer
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.2 No.5,
December
31,
2011
ABSTRACT: The implementation of individualized targeted therapy for metastatic colorectal cancer (mCRC), in addition to standard chemotherapeutic regimens, currently is a topic under debate. Approximately 35% - 45% of mCRC patients exhibit mutated KRAS, which is considered to be an independent predictor of poor response to treatment with epidermal growth factor receptor (EGFR) monoclonal antibody. However, only about 50% of patients with wild-type KRAS respond to anti-EGFR therapy. Two major EGFR-dependent signaling pathways, RAS-RAF-MAPK and PI3K-PTEN-AKT, may be involved in the poor response to anti-EGFR. Increased EGFR gene copy number as detected by fluorescence in situ hybridization, but not increased EGFR protein expression, correlates with efficacy of anti-EGFR treatment. The identification of mutations in BRAF and PIK3CA (exon 20) and deletions in PTEN also may help clinicians screen for anti-EGFR resistance in mCRC patients with wild-type KRAS. To guide health professionals through the realm of individualized targeted therapies for mCRC, we review recent progress on identifying negative predictors and prognostic markers of anti-EGFR treatment efficacy.