Anti-Egfr Therapy in Colorectal Cancer: How to Choose The Right Patient

Author(s): F. Meriggi, B. Di Biasi, C. Abeni, A. Zaniboni.

Journal Name: Current Drug Targets

Volume 10 , Issue 10 , 2009

Abstract:

The anti-epidermal growth factor receptor monoclonal antibodies cetuximab and panitumumab have established efficacy as single agent and in combination with chemotherapy in advanced colorectal cancer. However, only a small percentage of unselected patients (around 10%) are responsive to these costly agents. Mutations in the KRAS gene are associated with resistance to both cetuximab and panitumumab and account for approximately 30% to 40% of resistant patients. Nevertheless, having an intact KRAS is necessary but not sufficient to derive benefit from EGFR inhibition. Further, positive predictive markers that are currently being evaluated include an increase in EGFR gene copy number and additional data suggest that other EGFR downstream pathways such as the PI3K/PTEN/AKT/mTOR and JAK/STAT pathways are also important when considering mechanisms of EGFR antibody resistance. New data seem to support the role of BRAF mutational status. In addition, high mRNA levels of the EGFR-ligands Epiregulin and Amphiregulin have been associated with increased responsiveness to cetuximab. In this article we will review the available clinical and experimental data potentially useful for a better patients selection.

Keywords: Anti-EGFR Therapy, Cetuximab, Panitumumab, Colorectal Cancer, Tyrosine-Kinase, KRAS

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 10
ISSUE: 10
Year: 2009
Page: [1033 - 1040]
Pages: 8
DOI: 10.2174/138945009789577891
Price: $58

Article Metrics

PDF: 8