{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T11:45:37Z","timestamp":1781523937647,"version":"3.54.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9]]},"DOI":"10.1093\/carcin\/bgs203","type":"journal-article","created":{"date-parts":[[2012,6,13]],"date-time":"2012-06-13T20:46:34Z","timestamp":1339620394000},"page":"1782-1790","source":"Crossref","is-referenced-by-count":25,"title":["Sorafenib enhances the therapeutic efficacy of rapamycin in colorectal cancers harboring oncogenic KRAS and PIK3CA"],"prefix":"10.1093","volume":"33","author":[{"given":"Pat","family":"Gulhati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yekaterina Y","family":"Zaytseva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D","family":"Valentino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payton D","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Tae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Sasazuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senji","family":"Shirasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Y","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi L","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianli","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Mark","family":"Evers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,6,13]]},"reference":[{"key":"key\n\t\t\t\t20170521011252_CIT0001","first-page":"7426","article-title":"The phosphatidylinositol 3\u02b9-kinase p85alpha gene is an oncogene in human ovarian and colon tumors.","volume":"61","author":"Philp","year":"2001","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170521011252_CIT0002","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/carcin\/23.1.201","article-title":"AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis.","volume":"23","author":"Roy","year":"2002","journal-title":"Carcinogenesis"},{"key":"key\n\t\t\t\t20170521011252_CIT0003","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ccr.2007.05.008","article-title":"Defining the role of mTOR in cancer.","volume":"12","author":"Guertin","year":"2007","journal-title":"Cancer Cell"},{"key":"key\n\t\t\t\t20170521011252_CIT0004","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1309\/LWDY1AXHXUULNVHQ","article-title":"High-resolution melting analysis for rapid detection of KRAS, BRAF, and PIK3CA gene mutations in colorectal cancer.","volume":"130","author":"Simi","year":"2008","journal-title":"Am. J. Clin. Pathol."},{"key":"key\n\t\t\t\t20170521011252_CIT0005","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1210\/jc.2008-0273","article-title":"Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase\/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers.","volume":"93","author":"Liu","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"key\n\t\t\t\t20170521011252_CIT0006","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1046\/j.0022-202X.2004.22243.x","article-title":"Genetic interaction between NRAS and BRAF mutations and PTEN\/MMAC1 inactivation in melanoma.","volume":"122","author":"Tsao","year":"2004","journal-title":"J. Invest. Dermatol."},{"key":"key\n\t\t\t\t20170521011252_CIT0007","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1146\/annurev.biochem.68.1.913","article-title":"eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation.","volume":"68","author":"Gingras","year":"1999","journal-title":"Annu. Rev. Biochem."},{"key":"key\n\t\t\t\t20170521011252_CIT0008","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1126\/science.1106148","article-title":"Phosphorylation and regulation of Akt\/PKB by the rictor-mTOR complex.","volume":"307","author":"Sarbassov","year":"2005","journal-title":"Science"},{"key":"key\n\t\t\t\t20170521011252_CIT0009","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1158\/1078-0432.CCR-09-1249","article-title":"Targeted inhibition of mammalian target of \u2028rapamycin signaling inhibits tumorigenesis of colorectal cancer.","volume":"15","author":"Gulhati","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"key\n\t\t\t\t20170521011252_CIT0010","doi-asserted-by":"crossref","first-page":"pe24","DOI":"10.1126\/scisignal.267pe24","article-title":"The pharmacology of mTOR inhibition.","volume":"2","author":"Guertin","year":"2009","journal-title":"Sci. Signal."},{"key":"key\n\t\t\t\t20170521011252_CIT0011","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1158\/0008-5472.CAN-05-2925","article-title":"mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt.","volume":"66","author":"O\u2019Reilly","year":"2006","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170521011252_CIT0012","first-page":"3065","article-title":"Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer.","volume":"118","author":"Carracedo","year":"2008","journal-title":"J. Clin. Invest."},{"key":"key\n\t\t\t\t20170521011252_CIT0013","doi-asserted-by":"crossref","first-page":"7099","DOI":"10.1158\/0008-5472.CAN-04-1443","article-title":"BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF\/MEK\/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis.","volume":"64","author":"Wilhelm","year":"2004","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170521011252_CIT0014","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1158\/1535-7163.MCT-08-0013","article-title":"Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.","volume":"7","author":"Wilhelm","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"key\n\t\t\t\t20170521011252_CIT0015","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1634\/theoncologist.2007-0233","article-title":"Selected combination therapy with sorafenib: a review of clinical data and perspectives in advanced solid tumors.","volume":"13","author":"Dal Lago","year":"2008","journal-title":"Oncologist"},{"key":"key\n\t\t\t\t20170521011252_CIT0016","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00280-007-0639-9","article-title":"Safety and anti-tumor activity of sorafenib (Nexavar) in combination with other anti-cancer agents: a review of clinical trials.","volume":"61","author":"Takimoto","year":"2008","journal-title":"Cancer Chemother. Pharmacol."},{"key":"key\n\t\t\t\t20170521011252_CIT0017","doi-asserted-by":"crossref","first-page":"20315","DOI":"10.1073\/pnas.0810715105","article-title":"Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis.","volume":"105","author":"Rychahou","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"key\n\t\t\t\t20170521011252_CIT0018","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/jnci\/85.3.200","article-title":"Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer.","volume":"85","author":"Allred","year":"1993","journal-title":"J. Natl. Cancer Inst."},{"key":"key\n\t\t\t\t20170521011252_CIT0019","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1158\/0008-5472.CAN-10-4058","article-title":"mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways.","volume":"71","author":"Gulhati","year":"2011","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170521011252_CIT0020","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug combination studies and their synergy quantification using the Chou-Talalay method.","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res."},{"key":"key\n\t\t\t\t20170521011252_CIT0021","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.4161\/cc.3.10.1164","article-title":"Oncogenic mutations of PIK3CA in human cancers.","volume":"3","author":"Samuels","year":"2004","journal-title":"Cell Cycle"},{"key":"key\n\t\t\t\t20170521011252_CIT0022","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1126\/science.8465203","article-title":"Altered growth of human colon cancer cell lines disrupted at activated Ki-ras.","volume":"260","author":"Shirasawa","year":"1993","journal-title":"Science"},{"key":"key\n\t\t\t\t20170521011252_CIT0023","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nrd2130","article-title":"Discovery and development of sorafenib: a multikinase inhibitor for treating cancer.","volume":"5","author":"Wilhelm","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"key\n\t\t\t\t20170521011252_CIT0024","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.cell.2009.12.040","article-title":"Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF.","volume":"140","author":"Heidorn","year":"2010","journal-title":"Cell"},{"key":"key\n\t\t\t\t20170521011252_CIT0025","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature08833","article-title":"RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth.","volume":"464","author":"Hatzivassiliou","year":"2010","journal-title":"Nature"},{"key":"key\n\t\t\t\t20170521011252_CIT0026","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1158\/1078-0432.CCR-10-2061","article-title":"Two drug interaction studies of sirolimus in combination with sorafenib or sunitinib in patients with advanced malignancies.","volume":"17","author":"Gangadhar","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"key\n\t\t\t\t20170521011252_CIT0027","doi-asserted-by":"crossref","first-page":"4194","DOI":"10.1002\/cncr.25931","article-title":"A phase 1 study of everolimus and sorafenib for metastatic clear cell renal cell carcinoma.","volume":"117","author":"Harzstark","year":"2011","journal-title":"Cancer"},{"key":"key\n\t\t\t\t20170521011252_CIT0028","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1038\/jid.2008.44","article-title":"Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells.","volume":"128","author":"Lasithiotakis","year":"2008","journal-title":"J. Invest. Dermatol."},{"key":"key\n\t\t\t\t20170521011252_CIT0029","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.jhep.2009.03.028","article-title":"Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined sorafenib and rapamycin in vivo.","volume":"51","author":"Newell","year":"2009","journal-title":"J. Hepatol."},{"key":"key\n\t\t\t\t20170521011252_CIT0030","doi-asserted-by":"crossref","first-page":"5124","DOI":"10.1158\/1078-0432.CCR-07-4774","article-title":"Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma.","volume":"14","author":"Wang","year":"2008","journal-title":"Clin. Cancer Res."}],"container-title":["Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/carcin\/article-pdf\/33\/9\/1782\/17291346\/bgs203.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T09:21:43Z","timestamp":1503566503000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/carcin\/article-lookup\/doi\/10.1093\/carcin\/bgs203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,13]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2012,6,13]]},"published-print":{"date-parts":[[2012,9]]}},"URL":"https:\/\/doi.org\/10.1093\/carcin\/bgs203","relation":{},"ISSN":["1460-2180","0143-3334"],"issn-type":[{"value":"1460-2180","type":"electronic"},{"value":"0143-3334","type":"print"}],"subject":[],"published":{"date-parts":[[2012,6,13]]}}}