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Drug Discovery Case History

Research and innovation in the development of everolimus for oncology

, , PhD, , PhD, , PhD, , MD, , MD, , MD, , MD, , , , PhD & , MD show all
Pages 323-338 | Published online: 17 Feb 2011

Bibliography

  • Adams CP, Brantner VV. Estimating the cost of new drug development: is it really 802 million dollars? Health Aff (Millwood) 2006;25:420-8
  • AFINITOR (everolimus) tablets for oral administration. Initial U.S. Approval: 2009 [prescribing information]. East Hanover, New Jersey: Novartis Pharmaceuticals Corp.; October 2010
  • AFINITOR [summary of product Characteristics] [prescribing information]. West Sussex, United Kingdom: Novartis Europharm Limited; 2009
  • Sabers CJ, Martin MM, Brunn GJ, Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem 1995;270:815-22
  • Meric-Bernstam F, Gonzalez-Angulo AM. Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 2009;27:2278-87
  • Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 2006;124:471-84
  • Patel PH, Chadalavada RS, Chaganti RS, Motzer RJ. Targeting von Hippel-Lindau pathway in renal cell carcinoma. Clin Cancer Res 2006;12:7215-20
  • Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004;18:1926-45
  • Thomson AW, Turnquist HR, Raimondi G. Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol 2009;9:324-37
  • Jia G, Cheng G, Agrawal DK. Autophagy of vascular smooth muscle cells in atherosclerotic lesions. Autophagy 2007;3:63-4
  • Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov 2006;5:671-88
  • O'Reilly T, McSheehy PM. Biomarker development for the clinical activity of the mTOR inhibitor everolimus (RAD001): processes, limitations, and further proposals. Transl Oncol 2010;3:65-79
  • Sehgal SN, Baker H, Vezina C. Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. J Antibiot (Tokyo) 1975;28:727-32
  • Saunders RN, Metcalfe MS, Nicholson ML. Rapamycin in transplantation: a review of the evidence. Kidney Int 2001;59:3-16
  • Bennett MR. In-stent stenosis: pathology and implications for the development of drug eluting stents. Heart 2003;89:218-24
  • Douros J, Suffness M. New antitumor substances of natural origin. Cancer Treat Rev 1981;8:63-87
  • Houchens DP, Ovejera AA, Riblet SM, Slagel DE. Human brain tumor xenografts in nude mice as a chemotherapy model. Eur J Cancer Clin Oncol 1983;19:799-805
  • Eng CP, Sehgal SN, Vezina C. Activity of rapamycin (AY-22,989) against transplanted tumors. J Antibiot (Tokyo) 1984;37:1231-7
  • Novak-Hofer I, Thomas G. An activated S6 kinase in extracts from serum- and epidermal growth factor-stimulated Swiss 3T3 cells. J Biol Chem 1984;259:5995-6000
  • Jeno P, Ballou LM, Novak-Hofer I, Thomas G. Identification and characterization of a mitogen-activated S6 kinase. Proc Natl Acad Sci USA 1988;85:406-10
  • Kozma SC, Ferrari S, Bassand P, Cloning of the mitogen-activated S6 kinase from rat liver reveals an enzyme of the second messenger subfamily. Proc Natl Acad Sci USA 1990;87:7365-9
  • Jaeschke A, Hartkamp J, Saitoh M, Tuberous sclerosis complex tumor suppressor-mediated S6 kinase inhibition by phosphatidylinositide-3-OH kinase is mTOR independent. J Cell Biol 2002;159:217-24
  • Garami A, Zwartkruis FJ, Nobukuni T, Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol Cell 2003;11:1457-66
  • Lane HA, Wood JM, McSheehy PMJ, mTOR inhibitor RAD001 (Everolimus) has antiangiogenic/vascular properties distinct from a VEGFR tyrosine kinase inhibitor. Clin Cancer Res 2009;15:1612-22
  • Beuvink I, Boulay A, Fumagalli S, The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation. Cell 2005;120:747-59
  • Tanaka C, O'Reilly T, Kovarik JM, Identifying optimal biologic doses of everolimus (RAD001) in patients with cancer based on the modeling of preclinical and clinical pharmacokinetic and pharmacodynamic data. J Clin Oncol 2008;26:1596-602
  • Breuleux M, Klopfenstein M, Stephan C, Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition. Mol Cancer Ther 2009;8:742-53
  • Boulay A, Zumstein-Mecker S, Stephan C, Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells. Cancer Res 2004;64:252-61
  • O'Reilly T, McSheehy PM, Wartmann M, Evaluation of the mTOR inhibitor, everolimus, in combination with cytotoxic antitumor agents using human tumor models in vitro and in vivo. Anticancer Drugs 2011;22:58-78
  • Boulay A, Lane HA. The mammalian target of rapamycin kinase and tumor growth inhibition. Recent Results Cancer Res 2007;172:99-124
  • O'Reilly T, McSheehy PM, Kawai R, Comparative pharmacokinetics of RAD001 (everolimus) in normal and tumor-bearing rodents. Cancer Chemother Pharmacol 2010;65:625-39
  • Breuleux M, Lane HA. Drug combinations as a therapeutic approach for mTORC1 inhibitors in human cancer. In: Houghton PJ, Polunofsky VA, editors, Cancer drug discovery and development. MTOR pathway and MTOR inhibitors in cancer therapy. Humana Press; 2010. p. 149-78
  • Boulay A, Rudloff J, Ye J, Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. Clin Cancer Res 2005;11:5319-28
  • Treeck O, Wackwitz B, Haus U, Ortmann O. Effects of a combined treatment with mTOR inhibitor RAD001 and tamoxifen in vitro on growth and apoptosis of human cancer cells. Gynecol Oncol 2006;102:292-9
  • Manegold PC, Paringer C, Kulka U, Antiangiogenic therapy with mammalian target of rapamycin inhibitor RAD001 (Everolimus) increases radiosensitivity in solid cancer. Clin Cancer Res 2008;14:892-900
  • Kim KW, Hwang M, Moretti L, Autophagy upregulation by inhibitors of caspase-3 and mTOR enhances radiotherapy in a mouse model of lung cancer. Autophagy 2008;4:659-68
  • Shinohara ET, Cao C, Niermann K, Enhanced radiation damage of tumor vasculature by mTOR inhibitors. Oncogene 2005;24:5414-22
  • Lane HA, Breuleux M. Optimal targeting of the mTORC1 kinase in human cancer. Curr Opin Cell Biol 2009;21:219-29
  • O'Donnell A, Faivre S, Burris HA III, Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol 2008;26:1588-95
  • Tabernero J, Rojo F, Calvo E, Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol 2008;26:1603-10
  • Tobinai K, Ogura M, Maruyama D, Phase I study of the oral mammalian target of rapamycin inhibitor everolimus (RAD001) in Japanese patients with relapsed or refractory non-Hodgkin lymphoma. Int J Hematol 2010: DOI 10.1007/s12185-010-0707-5
  • Shiah HS, Chen CY, Hsiao CF, Randomized, phase I study of everolimus in patients with advanced HCC. Presented at 12th World Congress of Gastrointestinal Cancer; Barcelona, Spain; June 30 – July 3 2010
  • Zhu AX, Abrams TA, Miksad R, A phase I/II study of everolimus in advanced hepatocellular carcinoma. Presented at: International Liver Cancer Association Annual Conference; Montreal, Canada; 10 – 12 September 2010. Oral presentation 0-030
  • Campone M, Levy V, Bourbouloux E, Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours. Br J Cancer 2009;100:315-21
  • Awada A, Cardoso F, Fontaine C, The oral mTOR inhibitor RAD001 (everolimus) in combination with letrozole in patients with advanced breast cancer: results of a phase I study with pharmacokinetics. Eur J Cancer 2008;44:84-91
  • Yao JC, Phan AT, Chang DZ, Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II trial. J Clin Oncol 2008;26:4311-18
  • Meikle L, Pollizzi K, Egnor A, Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci 2008;28:5422-32
  • Pollizzi K, Malinowska-Kolodziej I, Stumm M, Equivalent benefit of mTORC1 blockade and combined PI3K-mTOR blockade in a mouse model of tuberous sclerosis. Mol Cancer 2009;8:38
  • Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med 2006;355:1345-56
  • Kwiatkowski DJ, Manning BD. Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Hum Mol Genet 2005;14(Spec No 2):R251-8
  • Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 2008;412:179-90
  • Adriaensen ME, Schaefer-Prokop CM, Stijnen T, Prevalence of subependymal giant cell tumors in patients with tuberous sclerosis and a review of the literature. Eur J Neurol 2009;16:691-6
  • Baskin HJ Jr. The pathogenesis and imaging of the tuberous sclerosis complex. Pediatr Radiol 2008;38:936-52
  • Franz DN, Brody A, Meyer C, Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med 2001;164:661-8
  • Krueger DA, Care MM, Holland K, Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 2010;363:1801-11
  • Franz DN, Leonard J, Tudor C, Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 2006;59:490-8
  • Wienecke R, Fackler I, Linsenmaier U, Antitumoral activity of rapamycin in renal angiomyolipoma associated with tuberous sclerosis complex. Am J Kidney Dis 2006;48:e27-9
  • Koenig MK, Butler IJ, Northrup H. Regression of subependymal giant cell astrocytoma with rapamycin in tuberous sclerosis complex. J Child Neurol 2008;23:1238-9
  • American Cancer Society. Kidney cancer (Adult) renal cell carcinoma overview. American Cancer Society Web site. Available from: http://www.cancer.org/Cancer/KidneyCancer/OverviewGuide/kidney-cancer–adult–renal-cell-carcinoma-overview-what-is-cancer
  • Linehan WM, Walther MM, Zbar B. The genetic basis of cancer of the kidney. J Urol 2003;170:2163-72
  • Pantuck AJ, Seligson DB, Klatte T, Prognostic relevance of the mTOR pathway in renal cell carcinoma: implications for molecular patient selection for targeted therapy. Cancer 2007;109:2257-67
  • Majumder PK, Febbo PG, Bikoff R, mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 2004;10:594-601
  • Amato RJ, Jac J, Giessinger S, A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer. Cancer 2009;115:2438-46
  • Motzer RJ, Escudier B, Oudard S, Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-56
  • Motzer RJ, Escudier B, Oudard S, Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 2010;116:4256-65
  • Calvo E, Motzer RJ, Hutson TE, Phase 3 record-1 study of everloimus in metastatic renal cell carcinoma (MRCC): subgroup analysis of patients (PTS) with 1 versus 2 prior vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) therapies [abstract]. Ann Oncol 2010;21(Suppl 8): viii285
  • Bracarda S, Escudier B, Porta C, Randomized, placebo-controlled, phase 3 study of everolimus in patients with metastatic renal cell carcinoma (MRCC): subgroup analysis of patients intolerant of prior vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) therapy [abstract]. Ann Oncol 2010;21(Suppl 8): viii292
  • Korhonen P, Malangone E. Overall survival (OS) of mRCC patients corrected for crossover using inverse probability of censoring weights (IPCW) and rank preserving structural failure time (RPSFT) models: two analyses from the RECORD-1 trial [abstract]. J Clin Oncol 2010;28(15 Suppl):4595
  • Hainsworth JD, Spigel DR, Burris HA III, Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma. J Clin Oncol 2010;28:2131-6
  • Jacobs C. Neuroendocrine tumors a rare finding: part I. Clin J Oncol Nurs 2009;13:21-3
  • von WG, Jehle PM, Hoeflich A, Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. Cancer Res 2000;60:4573-81
  • Papouchado B, Erickson LA, Rohlinger AL, Epidermal growth factor receptor and activated epidermal growth factor receptor expression in gastrointestinal carcinoids and pancreatic endocrine carcinomas. Mod Pathol 2005;18:1329-35
  • Perren A, Komminoth P, Saremaslani P, Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. Am J Pathol 2000;157:1097-103
  • Jensen RT, Berna MJ, Bingham DB, Norton JA. Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies. Cancer 2008;113(Suppl 7):1807-43
  • Hammel PR, Vilgrain V, Terris B, Pancreatic involvement in von Hippel-Lindau disease. The Groupe Francophone d'Etude de la Maladie de von Hippel-Lindau. Gastroenterology 2000;119:1087-95
  • Yao JC, Lombard-Bohas C, Baudin E, Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 2010;28:69-76
  • Yao JC, Shah MH, Ito C, A randomized, double blind, placebo-controlled, multicenter phase III trial of everolimus in patients with advanced pancreatic neuoendocrine tumors (pnet) (radiiant-3): viii4 (abstract LBA9) [abstract]. Ann Oncol 2010;21(Suppl 8): viii4
  • Pavel M, Hainsworth JD, Baudin E, A randomized, double blind, placebo-controlled,multicenter phase III trial of everolimus 1 octreotide lar vs placebo 1 octreotide in patients with advanced neuroendocrine tumors(net) (Radiant-2) [abstract]. Ann Oncol 2010;21(Suppl 8):4
  • Perez-Tenorio G, Stal O. Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer 2002;86:540-5
  • Johnston SR. Combinations of endocrine and biological agents: present status of therapeutic and presurgical investigations. Clin Cancer Res 2005;11:889s-899s
  • Ellard SL, Clemons M, Gelmon KA, Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163. J Clin Oncol 2009;27:4536-41
  • Baselga J, Semiglazov V, van DP, Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol 2009;27:2630-7
  • Witzig E, Habermann C, Reeder C, A phase II trial of the oral MTOR inhibitor everolimus in relapsed non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) [abstract]. Haematologica 2009;94(Suppl 2):436
  • Ghobrial IM, Gertz M, Laplant B, Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol 2010;28:1408-14
  • Decker T, Sandherr M, Goetze K, A pilot trial of the mTOR (mammalian target of rapamycin) inhibitor RAD001 in patients with advanced B-CLL. Ann Hematol 2009;88:221-7
  • Doi T, Muro K, Boku N, Multicenter phase II study of everolimus in patients with previously treated metastatic gastric cancer. J Clin Oncol 2010;28:1904-10
  • Yoon DH, Ryu M, Lee J, Phase II study of everolimus in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum [abstract]. Ann Oncol 2010;21(Suppl 8): viii229
  • Villanueva A, Chiang DY, Newell P, Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008;135:1972-83
  • Novartis Pharmaceuticals Corporation. Worldwide initiative to develop everolimus (WIDE) program. Novartis Oncology US Web Site. Available from: www.thewideprogram.com. [Accessed 13 January 2011]
  • National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in OncologyTM Kidney Cancer (Version 2.2010). 2010. Available from: http://www.nccn.org/index.asp. [Accessed 1 October 2010]
  • de Reijke TM, Bellmunt J, van PH, EORTC-GU group expert opinion on metastatic renal cell cancer. Eur J Cancer 2009;45:765-73
  • European Association of Urology. Guidelines on Renal Cell Carcinoma. 2009. Available from: http://www.uroweb.org. [Accessed 1 October 2010]
  • Grunwald V, Miller K, Machiels J, An international expanded access program (EAP) of everolimus in patients with metastatic renal cell carcinoma (MRCC) who are intolerant of or have progressed after prior vascular enothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR) therapy [abstract]. Ann Oncol 2010;21(Suppl 8): viii274
  • Hudes G, Carducci M, Tomczak P, Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-81
  • National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in OncologyTM Neuroendocrine Tumors. 2010. Available from: http://www.nccn.org/clinical.asp. [Accessed 1 October 2010]
  • Escudier B, Kataja V. Renal cell carcinoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol 2009;20(Suppl 4):81-2
  • Kidd M, Svejda B, Giovinazzo F, Effective inhibition of human neuroendocrine tumor cell proliferation by a TOR kinase inhibitor and a novel somatostatin receptor agonist, pasireotide [abstract]. Presented at 2010 American Association of Clinical Oncology Gastrointestinal Cancer Symposium; 22 – 24 January 2010; Orlando, FL
  • O'Reilly T, Vaxelaire J, Muller M. In vivo activity of RAD001, an orally active rapamycin derivative, in experimental tumor models [abstract]. Proc Am Assoc Cancer Res 2002;43:71
  • Wong M. Mammalian target of rapamycin (mTOR) inhibition as a potential antiepileptogenic therapy: from tuberous sclerosis to common acquired epilepsies. Epilepsia 2010;51:27-36
  • McBride KL, Varga EA, Pastore MT, Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly. Autism Res 2010;3:137-41
  • Caccamo A, Majumder S, Richardson A, Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J Biol Chem 2010;285:13107-20
  • Malagelada C, Jin ZH, Jackson-Lewis V, Rapamycin protects against neuron death in in vitro and in vivo models of Parkinson's disease. J Neurosci 2010;30:1166-75

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