Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: Beyond KRAS mutations

2013 ◽  
Vol 85 (1) ◽  
pp. 45-81 ◽  
Author(s):  
Ana Custodio ◽  
Jaime Feliu
Keyword(s):  
Colorectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Kras Mutations ◽  
Epidermal Growth

KRAS Mutations and Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Colorectal Cancer: Practical Application of Patient Selection

2009 ◽  
Vol 27 (7) ◽  
pp. 1130-1136 ◽  
Author(s):  
Antonio Jimeno ◽  
Wells A. Messersmith ◽  
Fred R. Hirsch ◽  
Wilbur A. Franklin ◽  
S. Gail Eckhardt
Keyword(s):  
Colorectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Drug Development ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Substantial Impact ◽  
Specificity And Sensitivity ◽  
Epidermal Growth

Recent retrospective evidence from several randomized studies has established that advanced colorectal cancer patients with tumors harboring a mutation in the KRAS gene do not derive benefit from the administration of epidermal growth factor receptor–directed monoclonal antibodies, such as cetuximab or panitumumab. This represents a paradigm-changing event and will have substantial impact on current and future anticancer drug development. These results add to the economic and ethical considerations involved in the development of novel targeted therapies and should increase our scrutiny of mechanisms of resistance and predictive biomarkers while in earlier developmental stages. In this article we will review the available clinical data, discuss the potential implications for future drug development in colorectal cancer, and provide a comprehensive overview of the technical aspects of KRAS mutation testing. In particular we aimed at enumerating the available procedures for mutation detection and their main characteristics, as well as comparing them from a clinical feasibility standpoint. While the true specificity and sensitivity of these methods have yet to be fully characterized, a better understanding of the differences between tests will be critical so that clinicians and pathologists can fully integrate this testing into the routine care of patients with colorectal cancer.

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