{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:36:22Z","timestamp":1773887782494,"version":"3.50.1"},"reference-count":23,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dig Dis"],"published-print":{"date-parts":[[2011]]},"abstract":"<jats:p>Mammalian target of rapamycin (mTOR) plays a central role in the regulation of cellular growth, proliferation, and survival via a cytoplasmic serine\/threonine kinase. mTOR also works as a nutrition sensor to monitor cellular metabolism. mTOR is located downstream in the PI3K\/Akt pathway, in which Akt and the tuberous sclerosis complex (TSC) 1\/2 are involved, to form a signal transduction pathway. New anticancer agents that target mTOR in the PI3K\/Akt pathway of the signal transduction pathways involved in cell proliferation control have recently been developed and are already commercially available. A phase III clinical trial of mTOR inhibitor for hepatocellular carcinoma (HCC) is now ongoing worldwide to expand indications. RAD001 is a signal-transduction inhibitor (STI) that targets mTOR (more specifically, mTORC1). mTORC1 signaling is intricately regulated by mitogens, growth factors, energy, and nutrients. mTORC1 is a regulator essential for general protein synthesis, located downstream of the PI3K\/AKT\/mTOR pathway, which is dysregulated in most human cancers. Inhibiting mTOR with molecules, such as RAD001, generates additive effects that accompany upstream and downstream target inhibition; alternatively, upstream receptor inhibition is compensated for by inhibiting the downstream pathway, even if some resistance develops against receptor inhibition regardless of initial or acquired resistance. In conclusion, RAD001 is a potential targeted agent for HCC and therefore final results of a phase III study are awaited.<\/jats:p>","DOI":"10.1159\/000327565","type":"journal-article","created":{"date-parts":[[2011,8,9]],"date-time":"2011-08-09T14:06:30Z","timestamp":1312898790000},"page":"310-315","source":"Crossref","is-referenced-by-count":17,"title":["mTOR Inhibitor for the Treatment of Hepatocellular Carcinoma"],"prefix":"10.1159","volume":"29","author":[{"given":"Masatoshi","family":"Kudo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2011,8,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.cell.2006.01.016"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038%2Fnrc1362"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016%2F0092-8674%2894%2990570-3"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016%2FS0092-8674%2800%2900117-3"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038%2Fnature04869"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038%2Fnature04871"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.270.22.13291"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1128%2FMCB.22.20.7004-7014.2002"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1158%2F1078-0432.CCR-06-2798"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038%2Fnm0202-128"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1002%2F%28SICI%291097-4652%28199902%29178%3A2%3C235%3A%3AAID-JCP13%3E3.0.CO%3B2-S"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1161%2Fhh1301.092506"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1158%2F1078-0432.CCR-03-0502"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016%2FS1471-4892%2803%2900071-7"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1200%2FJCO.2007.15.3700"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007%2F978-3-540-31209-3_7"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.onc.1208715"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1158%2F1078-0432.CCR-06-2770"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1158%2F0008-5472.CAN-06-4490"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1158%2F1078-0432.CCR-07-0955"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1158%2F1078-0432.CCR-04-0941"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jhep.2006.11.021"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1097%2F01.tp.0000252780.42104.95"}],"container-title":["Digestive Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/327565","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/327565","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T19:13:59Z","timestamp":1745435639000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000327565"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011]]},"references-count":23,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2011,8,1]]},"published-print":{"date-parts":[[2011,8,8]]}},"URL":"https:\/\/doi.org\/10.1159\/000327565","archive":["Portico"],"relation":{},"ISSN":["0257-2753","1421-9875"],"issn-type":[{"value":"0257-2753","type":"print"},{"value":"1421-9875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011]]}}}