{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:55:29Z","timestamp":1775148929773,"version":"3.50.1"},"reference-count":20,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T00:00:00Z","timestamp":1568678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0221994","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T17:23:22Z","timestamp":1568741002000},"page":"e0221994","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["A phase 2 study of an oral mTORC1\/mTORC2 kinase inhibitor (CC-223) for non-pancreatic neuroendocrine tumors with or without carcinoid symptoms"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3992-8722","authenticated-orcid":true,"given":"Edward","family":"Wolin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Mita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Mahipal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Bendell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Nemunaitis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pam N.","family":"Munster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Paz-Ares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen H.","family":"Filvaroff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Hege","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"de Haan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Mita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2019,9,17]]},"reference":[{"issue":"18","key":"pone.0221994.ref001","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1200\/JCO.2007.15.4377","article-title":"One hundred years after \"carcinoid\": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States","volume":"26","author":"JC Yao","year":"2008","journal-title":"J Clin Oncol"},{"key":"pone.0221994.ref002","unstructured":"National Cancer Institute. SEER Cancer Statistics Review 1975\u20132016 [Accessed May 3, 2019]. Available from: https:\/\/seer.cancer.gov\/csr\/1975_2016\/results_merged\/topic_prevcounts.pdf."},{"issue":"10022","key":"pone.0221994.ref003","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/S0140-6736(15)00817-X","article-title":"Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study","volume":"387","author":"JC Yao","year":"2016","journal-title":"Lancet"},{"issue":"6","key":"pone.0221994.ref004","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa1009290","article-title":"Everolimus for advanced pancreatic neuroendocrine tumors","volume":"364","author":"JC Yao","year":"2011","journal-title":"The New England journal of medicine"},{"issue":"2","key":"pone.0221994.ref005","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.18632\/oncotarget.13808","article-title":"Potentiation of the anticancer effects of everolimus using a dual mTORC1\/2 inhibitor in hepatocellular carcinoma cells","volume":"8","author":"JO Kim","year":"2017","journal-title":"Oncotarget"},{"issue":"3","key":"pone.0221994.ref006","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.eururo.2015.09.047","article-title":"Doubling Down on mTOR Inhibition: Harnessing ZEBRA for Insights.","volume":"69","author":"JY Chan","year":"2016","journal-title":"Eur Urol"},{"issue":"1","key":"pone.0221994.ref007","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1159\/000448843","article-title":"Inhibition of mTOR's Catalytic Site by PKI-587 Is a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease","volume":"105","author":"H Freitag","year":"2017","journal-title":"Neuroendocrinology"},{"issue":"6","key":"pone.0221994.ref008","doi-asserted-by":"crossref","first-page":"6576","DOI":"10.18632\/oncotarget.5878","article-title":"Dual mTOR inhibitor MLN0128 suppresses Merkel cell carcinoma (MCC) xenograft tumor growth.","volume":"7","author":"A Kannan","year":"2016","journal-title":"Oncotarget"},{"issue":"7","key":"pone.0221994.ref009","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1158\/1535-7163.MCT-15-0926","article-title":"Dual mTORC1\/2 Inhibition as a Novel Strategy for the Resensitization and Treatment of Platinum-Resistant Ovarian Cancer","volume":"15","author":"F Musa","year":"2016","journal-title":"Mol Cancer Ther"},{"issue":"4","key":"pone.0221994.ref010","first-page":"288","article-title":"Targeted Inhibition of Rictor\/mTORC2","volume":"16","author":"Z Zou","year":"2016","journal-title":"Cancer Treatment: A New Era after Rapamycin. Current cancer drug targets"},{"issue":"6","key":"pone.0221994.ref011","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1158\/1535-7163.MCT-14-1052","article-title":"CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization","volume":"14","author":"DS Mortensen","year":"2015","journal-title":"Mol Cancer Ther"},{"issue":"11","key":"pone.0221994.ref012","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1158\/1535-7163.MCT-17-0058","article-title":"mTOR Kinase Inhibition Effectively Decreases Progression of a Subset of Neuroendocrine Tumors that Progress on Rapalog Therapy and Delays Cardiac Impairment","volume":"16","author":"MA Orr-Asman","year":"2017","journal-title":"Mol Cancer Ther"},{"issue":"19","key":"pone.0221994.ref013","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1002\/cncr.29422","article-title":"A phase I dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1\/mTORC2 kinase inhibitor CC-223 in patients with advanced solid tumors or multiple myeloma","volume":"121","author":"JC Bendell","year":"2015","journal-title":"Cancer"},{"issue":"2","key":"pone.0221994.ref014","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).","volume":"45","author":"EA Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"issue":"2","key":"pone.0221994.ref015","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1214\/aoms\/1177731118","article-title":"Sequential tests of statistical hypotheses","volume":"16","author":"A Wald","year":"1945","journal-title":"Ann Math Statist"},{"issue":"15_suppl","key":"pone.0221994.ref016","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1200\/jco.2013.31.15_suppl.2606","article-title":"Phase I expansion trial of an oral TORC1\/TORC2 inhibitor (CC-223) in advanced solid tumors","volume":"31","author":"A Varga","year":"2013","journal-title":"Journal of Clinical Oncology"},{"issue":"7","key":"pone.0221994.ref017","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1634\/theoncologist.2015-0420","article-title":"Efficacy and Safety of Everolimus in Extrapancreatic Neuroendocrine Tumor: A Comprehensive Review of Literature","volume":"21","author":"A Faggiano","year":"2016","journal-title":"Oncologist"},{"issue":"3","key":"pone.0221994.ref018","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.trre.2014.03.002","article-title":"Strategies for the management of adverse events associated with mTOR inhibitors.","volume":"28","author":"B Kaplan","year":"2014","journal-title":"Transplant Rev (Orlando)."},{"key":"pone.0221994.ref019","volume-title":"The Clinical Pharmacology and Toxicity Profile of Rapalogs","author":"DW Su","year":"2016","edition":"1 ed"},{"issue":"11","key":"pone.0221994.ref020","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1634\/theoncologist.2015-0519","article-title":"Hyperglycemia Associated With Targeted Oncologic Treatment: Mechanisms and Management","volume":"21","author":"JW Goldman","year":"2016","journal-title":"Oncologist"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0221994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T03:30:59Z","timestamp":1611199859000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0221994"}},"subtitle":[],"editor":[{"given":"Dustin A.","family":"Deming","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2019,9,17]]},"references-count":20,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0221994","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,17]]}}}