Cetuximab in combination therapy: from bench to clinic.
Cetuximab, a chimeric IgG(1) monoclonal antibody directed against the ligand-binding domain of the epidermal growth factor receptor, offers a paradigm for the combination of molecularly targeted therapies with cytotoxic agents. In preclinical models, the addition of cetuximab to chemotherapy or radiation therapy enhances antitumor activity. Proposed mechanisms include reducing tumor cell proliferation, angiogenesis, and DNA repair capacity; increasing apoptosis; and inducing cell cycle arrest at treatment-sensitive points. These effects may enhance and restore tumor sensitivity to cytotoxic therapies. In clinical trials, the addition of cetuximab to chemotherapy improves outcomes of patients who had previously failed such agents, as illustrated in irinotecan-resistant and oxaliplatin-refractory metastatic colorectal cancer. As initial therapy, the addition of cetuximab to chemotherapy extends survival in colorectal cancer, lung cancer, and head and neck cancer. Combining cetuximab with radiation therapy extends survival in locally advanced head and neck cancer. As predictive biomarkers are identified, it may become possible to select patients most likely to benefit from such combinations.
Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Mail Code 8852, Dallas, TX, 75390-8852, USA. david.gerber@utsouthwestern.edu
David E
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D002986:Clinical Trials as Topic / Q000379:methods* / Q000639:trends; D003131:Combined Modality Therapy; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000639:trends; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D018773:Genes, erbB-1; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab