{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:33:38Z","timestamp":1791221618807,"version":"4.1.0"},"reference-count":10,"publisher":"American Association for Cancer Research (AACR)","issue":"6","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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 (\u201cxenopatients\u201d) 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. Cancer Discovery; 1(6); 472\u201374. \u00a92011 AACR.<\/jats:p>\n               <jats:p>Commentary on Bertotti et al., p. 508.<\/jats:p>","DOI":"10.1158\/2159-8290.cd-11-0261","type":"journal-article","created":{"date-parts":[[2011,11,17]],"date-time":"2011-11-17T13:40:20Z","timestamp":1321537220000},"page":"472-474","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["HER2 Signaling and Resistance to the Anti-EGFR Monoclonal Antibody Cetuximab: A Further Step toward Personalized Medicine for Patients with Colorectal Cancer"],"prefix":"10.1158","volume":"1","author":[{"given":"Fortunato","family":"Ciardiello","sequence":"first","affiliation":[{"name":"Authors' Affiliations:\u20081Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale \u201cF. Magrassi e A. Lanzara,\u201d Seconda Universit\u00e0 degli Studi di Napoli; and 2Cell Biology and Biotherapy Unit, INT-Fondazione \u201cG. Pascale,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Normanno","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale \u201cF. Magrassi e A. Lanzara,\u201d Seconda Universit\u00e0 degli Studi di Napoli; and 2Cell Biology and Biotherapy Unit, INT-Fondazione \u201cG. Pascale,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2011,11,16]]},"reference":[{"key":"2022060622124519500_bib1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/1040-8428(94)00144-I","article-title":"Epidermal growth factor-related peptides and their receptors in human malignancies","volume":"19","author":"Salomon","year":"1995","journal-title":"Crit Rev Oncol Hematol"},{"key":"2022060622124519500_bib2","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1056\/NEJMra0707704","article-title":"EGFR antagonists in cancer treatment","volume":"358","author":"Ciardiello","year":"2008","journal-title":"N Engl J Med"},{"key":"2022060622124519500_bib3","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrclinonc.2009.111","article-title":"Implications for KRAS status and EGFR-targeted therapies in metastatic CRC","volume":"6","author":"Normanno","year":"2009","journal-title":"Nat Rev Clin Oncol"},{"key":"2022060622124519500_bib4","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S1470-2045(10)70130-3","article-title":"Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis","volume":"11","author":"De Roock","year":"2010","journal-title":"Lancet Oncol"},{"key":"2022060622124519500_bib5","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1158\/2159-8290.CD-11-0109","article-title":"A molecularly annotated platform of patient-derived xenografts (\u2018xenopatients\u2019) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer","volume":"1","author":"Bertotti","year":"2011","journal-title":"Cancer Discovery"},{"key":"2022060622124519500_bib6","doi-asserted-by":"crossref","first-page":"99ra86","DOI":"10.1126\/scitranslmed.3002442","article-title":"Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab","volume":"3","author":"Yonesaka","year":"2011","journal-title":"Science Transl Med"},{"key":"2022060622124519500_bib7","first-page":"8887","article-title":"Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2\/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo","volume":"61","author":"Moulder","year":"2001","journal-title":"Cancer Res"},{"key":"2022060622124519500_bib8","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/annonc\/mdf020","article-title":"Cooperative inhibitory effect of ZD1839 (Iressa) in combination with trastuzumab (Herceptin) on human breast cancer cell growth","volume":"13","author":"Normanno","year":"2002","journal-title":"Ann Oncol"},{"key":"2022060622124519500_bib9","doi-asserted-by":"crossref","first-page":"6277","DOI":"10.1158\/1078-0432.CCR-08-0482","article-title":"A phase I-II study of combined blockade of the ErbB receptor network with trastuzumab and gefitinib in patients with HER2 (ErbB2)-overexpressing metastatic breast cancer","volume":"14","author":"Arteaga","year":"2008","journal-title":"Clin Cancer Res"},{"key":"2022060622124519500_bib10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10549-007-9830-2","article-title":"Breast cancer cells with acquired resistance to the EGFR tyrosine kinase inhibitor gefitinib show persistent activation of MAPK signaling","volume":"112","author":"Normanno","year":"2008","journal-title":"Breast Cancer Res Treat"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/1\/6\/472\/1848030\/472.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/1\/6\/472\/1848030\/472.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T22:12:58Z","timestamp":1654553578000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/1\/6\/472\/2330\/HER2-Signaling-and-Resistance-to-the-Anti-EGFR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,1]]},"references-count":10,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2011,11,16]]},"published-print":{"date-parts":[[2011,11,1]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-11-0261","relation":{},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11,1]]}}}