{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:04:55Z","timestamp":1791201895374,"version":"4.2.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,12,15]]},"DOI":"10.2146\/ajhp100020","type":"journal-article","created":{"date-parts":[[2010,11,30]],"date-time":"2010-11-30T10:24:26Z","timestamp":1291112666000},"page":"2095-2106","source":"Crossref","is-referenced-by-count":49,"title":["Mammalian target of rapamycin: Biological function and target for novel anticancer agents"],"prefix":"10.1093","volume":"67","author":[{"given":"Emily B.","family":"Borders","sequence":"first","affiliation":[{"name":"College of Pharmacy, University of Oklahoma, Oklahoma City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Bivona","sequence":"additional","affiliation":[{"name":"University of Kansas Hospital, Kansas City, KS; at the time of writing she was pharmacy student, College of Pharmacy, University of Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Medina","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Oklahoma"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"key\n\t\t\t\t2019041104345198000_b1-0672095","doi-asserted-by":"crossref","first-page":"7479","DOI":"10.1158\/1078-0432.CCR-09-0636","article-title":"Resistance to trastuzumab in breast cancer","volume":"15","author":"Polhmann","year":"2009","journal-title":"Clin Cancer"},{"key":"key\n\t\t\t\t2019041104345198000_b2-0672095","volume-title":"Rapamune (sirolimus) package insert","year":"2010"},{"key":"key\n\t\t\t\t2019041104345198000_b3-0672095","first-page":"627","article-title":"Targeting the phosphoinositide 3-kinase pathway in cancer","volume":"8","author":"Liu","year":"2009","journal-title":"Nature"},{"key":"key\n\t\t\t\t2019041104345198000_b4-0672095","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","article-title":"TOR signaling in growth and metabolism","volume":"124","author":"Wullschleger","year":"2006","journal-title":"Cell"},{"key":"key\n\t\t\t\t2019041104345198000_b5-0672095","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1200\/JCO.2008.20.0766","article-title":"Targeting the mTOR signaling network for cancer therapy","volume":"27","author":"Meric-Bernstam","year":"2009","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b6-0672095","first-page":"729","article-title":"mTOR and cancer: insights into a complex relationship","volume":"6","author":"Sabatini","year":"2006","journal-title":"Nature"},{"key":"key\n\t\t\t\t2019041104345198000_b7-0672095","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00018-009-0163-7","article-title":"Key factors in mTOR regulation","volume":"67","author":"Bai","year":"2010","journal-title":"Cell Mol Life Sci"},{"key":"key\n\t\t\t\t2019041104345198000_b8-0672095","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12154-008-0003-5","article-title":"Rapamycin and mTOR kinase inhibitors","volume":"1","author":"Ballou","year":"2008","journal-title":"J Chem Biol"},{"key":"key\n\t\t\t\t2019041104345198000_b9-0672095","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1093\/hmg\/ddn192","article-title":"Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1","volume":"17","author":"Rosner","year":"2008","journal-title":"Hum Mol Genet"},{"key":"key\n\t\t\t\t2019041104345198000_b10-0672095","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1200\/JCO.2004.02.141","article-title":"The biology and clinical relevance of the PTEN tumor suppressor pathway","volume":"22","author":"Sansal","year":"2004","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b11-0672095","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1081\/CNV-200027144","article-title":"The tuberous sclerosis complex genes in tumor development","volume":"22","author":"Mak","year":"2004","journal-title":"Cancer Invest"},{"key":"key\n\t\t\t\t2019041104345198000_b12-0672095","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1002\/cncr.22677","article-title":"Prognostic relevance of the mTOR pathway in renal cell carcinoma: implications for molecular patient selection for targeted therapy","volume":"109","author":"Pantuck","year":"2007","journal-title":"Cancer"},{"key":"key\n\t\t\t\t2019041104345198000_b13-0672095","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1002\/cncr.22195","article-title":"4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer","volume":"107","author":"Castellvi","year":"2006","journal-title":"Cancer"},{"key":"key\n\t\t\t\t2019041104345198000_b14-0672095","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\t2019041104345198000_b15-0672095","volume-title":"Torisel (temsirolimus) package insert","year":"2008"},{"key":"key\n\t\t\t\t2019041104345198000_b16-0672095","volume-title":"Afinitor (everolimus) package insert","year":"2009"},{"key":"key\n\t\t\t\t2019041104345198000_b17-0672095","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/1756-8722-2-45","article-title":"Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy","volume":"2","author":"Yuan","year":"2009","journal-title":"J Hematol Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b18-0672095","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3747\/co.v16i1.406","article-title":"Targeting mtor-dependent tumours with specific inhibitors: a model for personalized medicine based on molecular diagnoses","volume":"16","author":"Furic","year":"2009","journal-title":"Curr Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b19-0672095","doi-asserted-by":"crossref","first-page":"7081","DOI":"10.1021\/jm9012642","article-title":"Discovery of potent and selective inhibitors of the mammalian target of rapamycin (mTOR) kinase","volume":"52","author":"Nowak","year":"2009","journal-title":"J Med Chem"},{"key":"key\n\t\t\t\t2019041104345198000_b20-0672095","doi-asserted-by":"crossref","first-page":"7644","DOI":"10.1158\/0008-5472.CAN-09-0823","article-title":"Dual phosphoinositide 3-kinase\/mammalian target of rapamycin blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS mutations","volume":"69","author":"Konstantinidou","year":"2009","journal-title":"Cancer Res"},{"key":"key\n\t\t\t\t2019041104345198000_b21-0672095","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ccr.2004.06.022","article-title":"PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients","volume":"6","author":"Nagata","year":"2004","journal-title":"Cancer Cell"},{"issue":"suppl","key":"key\n\t\t\t\t2019041104345198000_b22-0672095","article-title":"Multicenter phase I clinical trial of daily and weekly RAD001 in combination with weekly paclitaxel and trastuzumab in patients with HER2-overexpressing metastatic breast cancer with prior resistance to trastuzumab","volume":"26","author":"Andre","year":"2008","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b23-0672095","doi-asserted-by":"crossref","first-page":"7266","DOI":"10.1158\/1078-0432.CCR-09-1665","article-title":"Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-over-expressing cancer cells","volume":"15","author":"Miller","year":"2009","journal-title":"Clin Cancer Res"},{"key":"key\n\t\t\t\t2019041104345198000_b24-0672095","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1093\/annonc\/mdp060","article-title":"Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors","volume":"20","author":"Soria","year":"2009","journal-title":"Ann Oncol"},{"issue":"suppl","key":"key\n\t\t\t\t2019041104345198000_b25-0672095","doi-asserted-by":"crossref","first-page":"7575","DOI":"10.1200\/jco.2007.25.18_suppl.7575","article-title":"Combined inhibition of mTOR and EGFR with everolimus (RAD001) and gefitinib in patients with non-small cell lung cancer who have smoked cigarettes: a phase II trial","volume":"25","author":"Kris","year":"2007","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b26-0672095","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1093\/annonc\/mdm170","article-title":"Akt-induced endocrine therapy resistance is reversed by inhibition of mTOR signaling","volume":"18","author":"Beeram","year":"2007","journal-title":"Ann Oncol"},{"issue":"suppl","key":"key\n\t\t\t\t2019041104345198000_b27-0672095","article-title":"Phase 3 study of temsirolimus with letrozole or letrozole alone in postmenopausal women with locally advanced or metastatic breast cancer","volume":"100","author":"Chow","year":"2006","journal-title":"Breast Cancer Res Treat"},{"key":"key\n\t\t\t\t2019041104345198000_b28-0672095","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ejca.2007.10.003","article-title":"The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: results of a phase I study with pharmacokinetics","volume":"44","author":"Awada","year":"2008","journal-title":"Eur J Cancer"},{"key":"key\n\t\t\t\t2019041104345198000_b29-0672095","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1200\/JCO.2008.18.8391","article-title":"Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer","volume":"27","author":"Baselga","year":"2009","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b30-0672095","unstructured":"NCT00863655: Everolimus in combination with exemestane in the treatment of postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer who are refractory to letrozole or anastrozole (BOLERO-2). http:\/clinicaltrials.gov\/ct2\/show\/NCT00863655?term=nct00863655&rank=1 (accessed 2010 Nov 2)."},{"key":"key\n\t\t\t\t2019041104345198000_b31-0672095","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1200\/JCO.2009.24.2669","article-title":"Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial","volume":"28","author":"Yao","year":"2009","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b32-0672095","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1158\/0008-5472.CAN-05-1189","article-title":"Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and inducing Zac1 expression","volume":"66","author":"Theodoropoulou","year":"2006","journal-title":"Cancer Res"},{"key":"key\n\t\t\t\t2019041104345198000_b33-0672095","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.cell.2004.12.040","article-title":"The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation","volume":"120","author":"Beuvink","year":"2005","journal-title":"Cell"},{"key":"key\n\t\t\t\t2019041104345198000_b34-0672095","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.1002\/cncr.24431","article-title":"Synergistic effect of rapamycin and cisplatin in endometrial cancer cells","volume":"115","author":"Bae-Jump","year":"2009","journal-title":"Cancer"},{"key":"key\n\t\t\t\t2019041104345198000_b35-0672095","doi-asserted-by":"crossref","first-page":"7031","DOI":"10.1158\/1078-0432.CCR-04-0361","article-title":"Targeting mammalian target of rapamycin synergistically enhances chemotherapy-induced cytotoxicity in breast cancer cells","volume":"10","author":"Mondesire","year":"2004","journal-title":"Clin Cancer Res"},{"key":"key\n\t\t\t\t2019041104345198000_b36-0672095","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1002\/cncr.23456","article-title":"Comparison of Akt\/mTOR signaling in primary breast tumors and matched distant metastases","volume":"112","author":"Akcakanat","year":"2008","journal-title":"Cancer"},{"key":"key\n\t\t\t\t2019041104345198000_b37-0672095","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1002\/cncr.24438","article-title":"Analysis of PTEN and HIF-1alpha and correlation with efficacy in patients with advanced renal cell carcinoma treated with temsirolimus versus interferon-alpha","volume":"115","author":"Figlin","year":"2009","journal-title":"Cancer"},{"key":"key\n\t\t\t\t2019041104345198000_b38-0672095","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3816\/CGC.2007.n.020","article-title":"Potential histologic and molecular predictors of response to temsirolimus in patients with advanced renal cell carcinoma","volume":"5","author":"Cho","year":"2007","journal-title":"Clin Genitourin Cancer"},{"key":"key\n\t\t\t\t2019041104345198000_b39-0672095","unstructured":"National Comprehensive Cancer Network. NCCN clinical practice guidelines in Oncology: Kidney cancer (v2.2010). www.nccn.org\/professionals\/physician_gls\/f_guidelines.asp (accessed 2010 Nov 2)."},{"key":"key\n\t\t\t\t2019041104345198000_b40-0672095","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1056\/NEJMoa066838","article-title":"Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma","volume":"356","author":"Hudes","year":"2007","journal-title":"N Engl J Med"},{"key":"key\n\t\t\t\t2019041104345198000_b41-0672095","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1200\/JCO.2004.08.185","article-title":"Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma","volume":"22","author":"Atkins","year":"2004","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b42-0672095","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1200\/JCO.1999.17.8.2530","article-title":"Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma","volume":"17","author":"Motzer","year":"1999","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b43-0672095","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1200\/JCO.2002.20.1.289","article-title":"Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma","volume":"20","author":"Motzer","year":"2002","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b44-0672095","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0140-6736(08)61039-9","article-title":"Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial","volume":"372","author":"Motzer","year":"2008","journal-title":"Lancet"},{"key":"key\n\t\t\t\t2019041104345198000_b45-0672095","doi-asserted-by":"crossref","first-page":"3822","DOI":"10.1200\/JCO.2008.20.7977","article-title":"Phase III study to evaluate temsirolimus compared with investigator\u2019s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma","volume":"27","author":"Hess","year":"2009","journal-title":"J Clin Oncol"},{"issue":"suppl","key":"key\n\t\t\t\t2019041104345198000_b46-0672095","first-page":"457S","article-title":"Activity of single agent temsirolimus (CCI-779) in non-mantle cell non-Hodgkin lymphoma subtypes","volume":"26","author":"Smith","year":"2008","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b47-0672095","first-page":"671","article-title":"Current development of mTOR inhibitors as anticancer agents","volume":"5","author":"Faivre","year":"2006","journal-title":"Nature"},{"key":"key\n\t\t\t\t2019041104345198000_b48-0672095","first-page":"892","article-title":"Correlation between loss of PTEN expression and Akt phosphorylation in endometrial carcinoma","volume":"7","author":"Kanamori","year":"2001","journal-title":"Clin Cancer Res"},{"issue":"suppl","key":"key\n\t\t\t\t2019041104345198000_b49-0672095","article-title":"A phase II study of oral mammalian target of rapamycin (mTOR) inhibitor, RAD001 (everolimus), in patients with recurrent endometrial carcinoma (EC)","volume":"26","author":"Slomovitz","year":"2008","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b50-0672095","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.1200\/JCO.2005.23.622","article-title":"Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study","volume":"23","author":"Galanis","year":"2005","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b51-0672095","first-page":"4573","article-title":"Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells","volume":"60","author":"Von Wichert","year":"2000","journal-title":"Cancer Res"},{"key":"key\n\t\t\t\t2019041104345198000_b52-0672095","article-title":"Temsirolimus i.v. monograph","volume-title":"AHFS drug information","author":"McEvoy","year":"2009"},{"key":"key\n\t\t\t\t2019041104345198000_b53-0672095","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1200\/JCO.2007.14.0988","article-title":"Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors","volume":"26","author":"O\u2019Donnell","year":"2008","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b54-0672095","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1200\/JCO.2004.08.116","article-title":"Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer","volume":"22","author":"Raymond","year":"2004","journal-title":"J Clin Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b55-0672095","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s11523-009-0107-z","article-title":"The emerging safety profile of mTOR inhibitors, a novel class of anticancer agents","volume":"4","author":"Sankhala","year":"2009","journal-title":"Target Oncol"},{"key":"key\n\t\t\t\t2019041104345198000_b56-0672095","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.ejca.2006.03.015","article-title":"Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus","volume":"42","author":"Duran","year":"2006","journal-title":"Eur J Cancer"},{"key":"key\n\t\t\t\t2019041104345198000_b57-0672095","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1097\/00007890-200109150-00008","article-title":"Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients","volume":"72","author":"Morelon","year":"2001","journal-title":"Transplantation"},{"key":"key\n\t\t\t\t2019041104345198000_b58-0672095","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1097\/01.TP.0000118413.92211.B6","article-title":"Sirolimus-associated pulmonary toxicity","volume":"77","author":"Pham","year":"2004","journal-title":"Transplantation"},{"key":"key\n\t\t\t\t2019041104345198000_b59-0672095","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1634\/theoncologist.2008-0120","article-title":"Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies","volume":"13","author":"Hutson","year":"2008","journal-title":"Oncologist"},{"key":"key\n\t\t\t\t2019041104345198000_b60-0672095","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1524-4733.2009.00617.x","article-title":"Cost-effectiveness of temsirolimus for first line treatment of advanced renal cell carcinoma","volume":"13","author":"Hoyle","year":"2009","journal-title":"Value Health"},{"key":"key\n\t\t\t\t2019041104345198000_b61-0672095","first-page":"HS-20","article-title":"Newly approved mTOR inhibitors for the treatment of metastatic renal cell carcinoma","volume":"34","author":"Cauley","year":"2009","journal-title":"US Pharm"}],"container-title":["American Journal of Health-System Pharmacy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ajhp\/article-pdf\/67\/24\/2095\/28345373\/ajhp2095.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T10:40:49Z","timestamp":1636886449000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajhp\/article\/67\/24\/2095\/5129954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,12,15]]},"references-count":61,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2010,12,15]]}},"URL":"https:\/\/doi.org\/10.2146\/ajhp100020","relation":{},"ISSN":["1079-2082","1535-2900"],"issn-type":[{"value":"1079-2082","type":"print"},{"value":"1535-2900","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,12,15]]},"published":{"date-parts":[[2010,12,15]]}}}