title: HER2 signaling and resistance to the anti-EGFR monoclonal antibody cetuximab: a further step toward personalized medicine for patients with colorectal cancer.
abstract: Primary and acquired resistance to anti-epidermal growth factor receptor (EGFR) drugs are clinically relevant problems in patients with metastatic colorectal carcinoma. A complex network of molecular alterations is involved in this phenomenon. Bertotti et al. report the development of serially transplantable groups of tumor xenografts in immune-deficient mice from patient-derived, genetically characterized metastatic colorectal carcinoma samples. These experimental models ("xenopatients") might represent a novel approach to discover and characterize the mechanisms of resistance to anti-EGFR therapy and other molecularly targeted therapies in metastatic colorectal carcinoma. In this respect, Bertotti et al. were able to identify HER2 gene amplification as one such mechanism of resistance to anti-EGFR therapy.
authors.affiliation: Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale F. Magrassi e A. Lanzara, Seconda Università degli Studi di Napoli, Italy. fortunato.ciardiello@unina2.it
authors.forename: Fortunato
authors.initials: F
authors.lastname: Ciardiello
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human