Abstract
Cetuximab is a chimeric monoclonal antibody that has revolutionized the treatment of metastatic colorectal cancer. Knowledge of the mechanisms that underlie its effectiveness, as well as the primary and secondary resistance mechanisms, have led to important developments in the understanding of cetuximab biology. In light of knowledge gained from recent trials, the efficacy of cetuximab has been clearly demonstrated to depend upon RAS mutational status, moreover cetuximab should only be used in a subset of patients who may benefit. In this article, we critically review clinical and pharmacogenetic issues of cetuximab, focusing on the cost-effectiveness involved with the use of the drug.
Keywords:
EGFR; RAS; cetxuximab; colorectal carcinoma; cost–effectiveness; pharmacogenomics; predictive; resistance.
MeSH terms
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Antibodies, Monoclonal, Humanized / therapeutic use*
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Antineoplastic Agents / therapeutic use*
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Cetuximab
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / pathology
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Drug Resistance, Neoplasm
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / physiology
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Humans
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Mutation
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Neoplasm Metastasis
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PTEN Phosphohydrolase / physiology
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Pharmacogenetics*
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Phosphatidylinositol 3-Kinases / physiology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins B-raf / genetics
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Proto-Oncogene Proteins B-raf / physiology
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Proto-Oncogene Proteins c-akt / physiology
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Proto-Oncogene Proteins p21(ras)
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TOR Serine-Threonine Kinases / physiology
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ras Proteins / genetics
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ras Proteins / physiology
Substances
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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KRAS protein, human
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Proto-Oncogene Proteins
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MTOR protein, human
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ErbB Receptors
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BRAF protein, human
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Proto-Oncogene Proteins B-raf
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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PTEN Phosphohydrolase
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PTEN protein, human
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Proto-Oncogene Proteins p21(ras)
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ras Proteins
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Cetuximab