title: KRAS mutations and susceptibility to cetuximab and panitumumab in colorectal cancer.
abstract: 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.
authors.affiliation: University of Colorado Cancer Center, Denver, CO, USA. Antonio.Jimeno@UCDenver.edu
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimeno
authors.forename: Wells A
authors.initials: WA
authors.lastname: Messersmith
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Franklin
authors.forename: S Gail
authors.initials: SG
authors.lastname: Eckhardt
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000187:drug effects* / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D000077544:Panitumumab; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005819:Genetic Markers; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077544:Panitumumab; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab