{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:06:38Z","timestamp":1791173198102,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T00:00:00Z","timestamp":1400025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"European Community's Seventh Framework Programme","award":["259015COLTHERES"],"award-info":[{"award-number":["259015COLTHERES"]}]},{"DOI":"10.13039\/501100005010","name":"AIRC","doi-asserted-by":"crossref","award":["12812"],"award-info":[{"award-number":["12812"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"name":"AIRC MFAG","award":["11349"],"award-info":[{"award-number":["11349"]}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:p>Cetuximab and panitumumab are anti\u2010epidermal growth factor receptor (anti\u2010EGFR) monoclonal antibodies used as therapies for metastatic colorectal cancer patients. Intrinsic mechanisms of resistance, such as RAS mutations, can prevent patients from having a response with clinical benefit. The clinical efficacy of EGFR targeted antibodies is limited by the development of acquired (secondary) resistance, which typically occurs within 3\u201312 months from the start of therapy. Preclinical models and analyses of clinical samples have uncovered some of the alterations that confer a selective advantage to tumor cells when under the pressure of anti\u2010EGFR therapy. Molecular profiling of clinical specimens confirmed that genetic alterations of genes in the EGFR\u2010RAS\u2010RAF\u2010MEK signaling pathway and of receptor tyrosine kinases are mechanisms of acquired resistance to anti\u2010EGFR antibodies. The escape from anti\u2010EGFR blockade appears to converge on the (re)activation of MEK\u2010ERK or AKT as revealed in preclinical studies. Circulating tumor DNA and patient derived xenografts have proven useful tools to monitor patients for resistance to anti\u2010EGFR therapy and test combination therapies to overcome or reverse resistance.<\/jats:p>","DOI":"10.1016\/j.molonc.2014.05.003","type":"journal-article","created":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T17:32:05Z","timestamp":1400088725000},"page":"1084-1094","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":140,"title":["Acquired resistance to EGFR\u2010targeted therapies in\u00a0colorectal cancer"],"prefix":"10.1002","volume":"8","author":[{"given":"Beth O.","family":"Van Emburgh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sartore-Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Di Nicolantonio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Siena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Bardelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.9273"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.7116"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0558"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4158"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-11-0109"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007094"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4905"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61649-9"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-1100-03"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033025"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70130-3"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11219"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305275"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1141478"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.26340"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1210093"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604009"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113205"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.8135"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071834"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804385"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044238"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.6796"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.03.003"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-0568"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-0191"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0589"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt010"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2013.31.15_suppl.tps3648"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204082"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007947"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11156"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2609"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(05)70102-9"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12065"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020073"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcpr.1998.0185"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2011-200353"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2466"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.5956"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0119"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25193"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds236"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-4136"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21149"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21166"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605534"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112302"},{"key":"e_1_2_11_50_1","first-page":"LBA 17","article-title":"Analysis of KRAS\/NRAS and BRAF mutations in FIRE-3: a randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients","volume":"49","author":"Stintzing S.","year":"2013","journal-title":"Eur. J. Cance."},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0108"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808268"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0423"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28106"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805019"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.08.1620"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.8.8.7903"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002442"}],"container-title":["Molecular Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.molonc.2014.05.003","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.molonc.2014.05.003","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S1574789114000969?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S1574789114000969?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.molonc.2014.05.003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T09:51:55Z","timestamp":1695462715000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1016\/j.molonc.2014.05.003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,14]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1016\/j.molonc.2014.05.003"],"URL":"https:\/\/doi.org\/10.1016\/j.molonc.2014.05.003","archive":["Portico"],"relation":{},"ISSN":["1574-7891","1878-0261"],"issn-type":[{"value":"1574-7891","type":"print"},{"value":"1878-0261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,14]]},"assertion":[{"value":"2014-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-05-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-05-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}