Abstract
Among the targeted therapies used in the treatment of metastatic colorectal cancer (CRC), cetuximab was registered in France in 2004. This chimeric antibody inhibiting the Epidermal Growth receptor (EGFR) has been demonstrated to be efficient in the treatment of irinotecan-resistant metastatic CRC expressing the EGFR. Panitumumab, a fully humanized anti-EGFR antibody should soon be registered after failure of conventional chemotherapies. However, these costly and potentially toxic treatments are efficient in a little proportion of patients. It is so necessary to identify some factors able to better define whose patients will benefit from these treatments. The major potential predictive factors of response to cetuximab and/or panitumumab that have been evaluated in the literature, which are summarized in this review, are molecular factors involved more or less directly in the EGF signaling pathway. Among them, KRAS mutations, EGFR gene copy number and, more recently, epiregulin and amphiregulin expression are those, along with skin toxicity, which appear to be the most relevant and which will have to be evaluated in future clinical trials to be validated before being incorporated in therapeutic strategy of CRC.
MeSH terms
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Amphiregulin
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / therapeutic use*
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Camptothecin / analogs & derivatives
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Camptothecin / therapeutic use
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Cetuximab
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / genetics*
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Cyclin D1 / genetics
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Drug Eruptions / etiology
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Drug Resistance, Neoplasm
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EGF Family of Proteins
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Epidermal Growth Factor / genetics
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Epidermal Growth Factor / metabolism
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Epiregulin
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / genetics
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Gene Dosage
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Glycoproteins / metabolism
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Humans
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Intercellular Signaling Peptides and Proteins / metabolism
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Irinotecan
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Mutation / genetics
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / genetics
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Panitumumab
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Polymorphism, Genetic
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins p21(ras)
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Receptors, IgG / genetics
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Vascular Endothelial Growth Factor A / metabolism
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ras Proteins / genetics
Substances
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AREG protein, human
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Amphiregulin
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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EGF Family of Proteins
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EREG protein, human
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Epiregulin
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FCGR2A protein, human
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FCGR3A protein, human
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Glycoproteins
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Intercellular Signaling Peptides and Proteins
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KRAS protein, human
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Receptors, IgG
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Vascular Endothelial Growth Factor A
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Cyclin D1
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Epidermal Growth Factor
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Panitumumab
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Irinotecan
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ErbB Receptors
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Proto-Oncogene Proteins p21(ras)
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ras Proteins
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Cetuximab
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Camptothecin