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
Current Drug Targets
Title: Anti-Egfr Therapy in Colorectal Cancer: How to Choose The Right Patient
Volume: 10 Issue: 10
Author(s): F. Meriggi, B. Di Biasi, C. Abeni and A. Zaniboni
Affiliation:
Keywords: Anti-EGFR Therapy, Cetuximab, Panitumumab, Colorectal Cancer, Tyrosine-Kinase, KRAS
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.
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Meriggi F., Di Biasi B., Abeni C. and Zaniboni A., Anti-Egfr Therapy in Colorectal Cancer: How to Choose The Right Patient, Current Drug Targets 2009; 10 (10) . https://dx.doi.org/10.2174/138945009789577891
DOI https://dx.doi.org/10.2174/138945009789577891 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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