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KRAS Mutations and Susceptibility to Cetuximab and Panitumumab in Colorectal Cancer

Jimeno, Antonio MD, PhD; Messersmith, Wells A. MD; Hirsch, Fred R. MD, PhD; Franklin, Wilbur A. MD; Eckhardt, S Gail MD

doi: 10.1097/PPO.0b013e31819e3202
Practice of Oncology: Recent Advances

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 and discuss the implications for future drug development in colorectal cancer.

From the University of Colorado Cancer Center, Denver, CO.

Reprints: Antonio Jimeno, MD, PhD, Medical Oncology Division, PO box 6511, MS 8117, Aurora, CO 80045. E-mail: Antonio.Jimeno@UCDenver.edu.

© 2009 Lippincott Williams & Wilkins, Inc.