Mammalian target of rapamycin inhibition in hepatocellular carcinoma

World Journal of Hepatology

Volumn 6, Issue 11, 2014, Pages 776-782

  Ashworth, René E ^a   Wu, Jennifer ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

CC 223; Everolimus; Hepatocellular carcinoma; Liver transplantation; Mammalian target of rapamycin; Mammalian target of rapamycin complex 1; Mammalian target of rapamycin complex 2; PI3K AKT mTOR signaling pathway; Sirolimus; Sorafenib

Indexed keywords

EID: 84911997235     PISSN: None     EISSN: 19485182     Source Type: Journal    
DOI: 10.4254/wjh.v6.i11.776     Document Type: Article

References (41)

1. Surveillance, Epidemiology, and End Results (SEER) Program SEER Stat Database: Incidence - SEER 17 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Linked To County Attributes - Total U.S., 1969-2007 Counties [database on the Internet] (Released April 2010, based on the November 2009 submission (1973-2007 varying) cited). Available from: URL: http://www.seer.cancer.gov
2. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-390 [PMID: 18650514 DOI: 10.1056/NEJMoa0708857]
3. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009; 10: 25-34 [PMID: 19095497 DOI: 10.1016/S1470-2045(08)70285-7]
4. Zhou L, Huang Y, Li J, Wang Z. The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinoma. Med Oncol 2010; 27: 255-261 [PMID: 19301157 DOI: 10.1007/s12032-009-9201-4]
5. Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, Brown M, Fitzgerald KJ, Sabatini DM. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell 2006; 11: 859-871 [PMID: 17141160 DOI: 10.1016/j.devcel.2006.10.007]
6. Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell 2009; 137: 873-886 [PMID: 19446321 DOI: 10.1016/j.cell.2009.03.046]
7. Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci 2009; 122: 3589-3594 [PMID: 19812304 DOI: 10.1242/jcs.051011]
8. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 2002; 110: 177-189 [PMID: 12150926 DOI: 10.1016/S0092-8674(02)00833-4]
9. Wang L, Harris TE, Roth RA, Lawrence JC. PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding. J Biol Chem 2007; 282: 20036-20044 [PMID: 17510057 DOI: 10.1074/jbc. M702376200]
10. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011; 12: 21-35 [PMID: 21157483 DOI: 10.1038/nrm3025]
11. Finn RS. Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition. Liver Cancer 2012; 1: 247-256 [PMID: 24159589 DOI: 10.1159/000343839]
12. Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS, Workman P. Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr Opin Pharmacol 2008; 8: 393-412 [PMID: 18721898 DOI: 10.1016/j.coph.2008.08.004]
13. Bayascas JR, Alessi DR. Regulation of Akt/PKB Ser473 phosphorylation. Mol Cell 2005; 18: 143-145 [PMID: 15837416 DOI: 10.1016/j.molcel.2005.03.020]
14. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006; 22: 159-168 [PMID: 16603397 DOI: 10.1016/j.molcel.2006.03.029]
15. Watanabe S, Horie Y, Kataoka E, Sato W, Dohmen T, Ohshima S, Goto T, Suzuki A. Non-alcoholic steatohepatitis and hepatocellular carcinoma: lessons from hepatocyte-specific phosphatase and tensin homolog (PTEN)-deficient mice. J Gastroenterol Hepatol 2007; 22 Suppl 1: S96-S100 [PMID: 17567478 DOI: 10.1111/j.1440-1746.2006.04665.x]
16. Wang L, Wang WL, Zhang Y, Guo SP, Zhang J, Li QL. Epigenetic and genetic alterations of PTEN in hepatocellular carcinoma. Hepatol Res 2007; 37: 389-396 [PMID: 17441812 DOI: 10.1111/j.1872-034X.2007.00042.x]
17. Rosner M, Hanneder M, Siegel N, Valli A, Fuchs C, Hengstschläger M. The mTOR pathway and its role in human genetic diseases. Mutat Res 2008; 659: 284-292 [PMID: 18598780 DOI: 10.1016/j.mrrev.2008.06.001]
18. Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 2008; 412: 179-190 [PMID: 18466115 DOI: 10.1042/BJ20080281]
19. Menon S, Yecies JL, Zhang HH, Howell JJ, Nicholatos J, Harputlugil E, Bronson RT, Kwiatkowski DJ, Manning BD. Chronic activation of mTOR complex 1 is sufficient to cause hepatocellular carcinoma in mice. Sci Signal 2012; 5: ra24 [PMID: 22457330 DOI: 10.1126/scisignal.2002739]
20. Logue JS, Morrison DK. Complexity in the signaling network: insights from the use of targeted inhibitors in cancer therapy. Genes Dev 2012; 26: 641-650 [PMID: 22474259 DOI: 10.1101/gad.186965.112]
21. Nissen NN, Menon V, Bresee C, Tran TT, Annamalai A, Poordad F, Fair JH, Klein AS, Boland B, Colquhoun SD. Recurrent hepatocellular carcinoma after liver transplant: identifying the high-risk patient. HPB (Oxford) 2011; 13: 626-632 [PMID: 21843263 DOI: 10.1111/j.1477-2574.2011.00342.x]
22. Freise CE, Ferrell L, Liu T, Ascher NL, Roberts JP. Effect of systemic cyclosporine on tumor recurrence after liver transplantation in a model of hepatocellular carcinoma. Transplantation 1999; 67: 510-513 [PMID: 10071018 DOI: 10.1097/00007890-199902270-00003]
23. Schumacher G, Oidtmann M, Rosewicz S, Langrehr J, Jonas S, Mueller AR, Rueggeberg A, Neuhaus R, Bahra M, Jacob D, Gerlach H, Neuhaus P. Sirolimus inhibits growth of human hepatoma cells in contrast to tacrolimus which promotes cell growth. Transplant Proc 2002; 34: 1392-1393 [PMID: 12176410 DOI: 10.1016/S0041-1345(02)02899-3]
24. Torimura T, Sata M, Ueno T, Kin M, Tsuji R, Suzaku K, Hashimoto O, Sugawara H, Tanikawa K. Increased expression of vascular endothelial growth factor is associated with tumor progression in hepatocellular carcinoma. Hum Pathol 1998; 29: 986-991 [PMID: 9744316 DOI: 10.1016/S0046-8177(98)90205-2]
25. Monaco AP. The role of mTOR inhibitors in the management of posttransplant malignancy. Transplantation 2009; 87: 157-163 [PMID: 19155967 DOI: 10.1097/TP.0b013e318193886e]
26. Toso C, Meeberg GA, Bigam DL, Oberholzer J, Shapiro AM, Gutfreund K, Ma MM, Mason AL, Wong WW, Bain VG, Kneteman NM. De novo sirolimus-based immunosuppression after liver transplantation for hepatocellular carcinoma: long-term outcomes and side effects. Transplantation 2007; 83: 1162-1168 [PMID: 17496530 DOI: 10.1097/01. tp.0000262607.95372.e0]
27. Menon KV, Hakeem AR, Heaton ND. Meta-analysis: recurrence and survival following the use of sirolimus in liver transplantation for hepatocellular carcinoma. Aliment Pharmacol Ther 2013; 37: 411-419 [PMID: 23278125 DOI: 10.1111/apt.12185]
28. Schnitzbauer AA, Zuelke C, Graeb C, Rochon J, Bilbao I, Burra P, de Jong KP, Duvoux C, Kneteman NM, Adam R, Bechstein WO, Becker T, Beckebaum S, Chazouillères O, Cillo U, Colledan M, Fändrich F, Gugenheim J, Hauss JP, Heise M, Hidalgo E, Jamieson N, Königsrainer A, Lamby PE, Lerut JP, Mäkisalo H, Margreiter R, Mazzaferro V, Mutzbauer I, Otto G, Pageaux GP, Pinna AD, Pirenne J, Rizell M, Rossi G, Rostaing L, Roy A, Turrion VS, Schmidt J, Troisi RI, van Hoek B, Valente U, Wolf P, Wolters H, Mirza DF, Scholz T, Steininger R, Soderdahl G, Strasser SI, Jauch KW, Neuhaus P, Schlitt HJ, Geissler EK. A prospective randomised, openlabeled, trial comparing sirolimus-containing versus mTORinhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma. BMC Cancer 2010; 10: 190 [PMID: 20459775 DOI: 10.1186/1471-2407-10-190]
29. Chen L, Shiah HS, Chen CY, Lin YJ, Lin PW, Su CW, and Chang JY. Randomized, phase I, and pharmacokinetic (PK) study of RAD001, and mTOR inhibitor, in patients (pts) with advanced hepatocellular carcinoma (HCC). J Clin Oncol (Meeting Abstracts) 2009; 27 (15S): 4587
30. Zhu AX, Abrams TA, Miksad R, Blaszkowsky LS, Meyerhardt JA, Zheng H, Muzikansky A, Clark JW, Kwak EL, Schrag D, Jors KR, Fuchs CS, Iafrate AJ, Borger DR, Ryan DP. Phase 1/2 study of everolimus in advanced hepatocellular carcinoma. Cancer 2011; 117: 5094-5102 [PMID: 21538343 DOI: 10.1002/cncr.26165]
31. Kneteman NM, Oberholzer J, Al Saghier M, Meeberg GA, Blitz M, Ma MM, Wong WW, Gutfreund K, Mason AL, Jewell LD, Shapiro AM, Bain VG, Bigam DL. Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma. Liver Transpl 2004; 10: 1301-1311 [PMID: 15376305 DOI: 10.1002/lt.20237]
32. Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, Poon RT, Blanc JF, Vogel A, Chen CL, Dorval E, Peck-Radosavljevic M, Santoro A, Daniele B, Furuse J, Jappe A, Perraud K, Anak O, Sellami DB, Chen LT. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA 2014; 312: 57-67 [PMID: 25058218 DOI: 10.1001/jama.2014.7189]
33. Breuleux M, Klopfenstein M, Stephan C, Doughty CA, Barys L, Maira SM, Kwiatkowski D, Lane HA. 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: 742-753 [PMID: 19372546 DOI: 10.1158/1535-7163.MCT-08-0668]
34. Finn RS, Poon RT, Yau T, Klümpen HJ, Chen LT, Kang YK, Kim TY, Gomez-Martin C, Rodriguez-Lope C, Kunz T, Paquet T, Brandt U, Sellami D, Bruix J. Phase I study investigating everolimus combined with sorafenib in patients with advanced hepatocellular carcinoma. J Hepatol 2013; 59: 1271-1277 [PMID: 23928403 DOI: 10.1016/j.jhep.2013.07.029]
35. De Simone P, Crocetti L, Pezzati D, Bargellini I, GhinolfiD, Carrai P, Leonardi G, Della Pina C, Cioni D, Pollina L, Campani D, Bartolozzi C, Lencioni R, Filipponi F. Efficacy and safety of combination therapy with everolimus and sorafenib for recurrence of hepatocellular carcinoma after liver transplantation. Transplant Proc 2014; 46: 241-244 [PMID: 24507059 DOI: 10.1016/j.transproceed.2013.10.035]
36. Ekim B, Magnuson B, Acosta-Jaquez HA, Keller JA, Feener EP, Fingar DC. mTOR kinase domain phosphorylation promotes mTORC1 signaling, cell growth, and cell cycle progression. Mol Cell Biol 2011; 31: 2787-2801 [PMID: 21576368 DOI: 10.1128/MCB.05437-11]
37. Shao H, Gao C, Tang H, Zhang H, Roberts LR, Hylander BL, Repasky EA, Ma WW, Qiu J, Adjei AA, Dy GK, Yu C. Dual targeting of mTORC1/C2 complexes enhances histone deacetylase inhibitor-mediated anti-tumor efficacy in primary HCC cancer in vitro and in vivo. J Hepatol 2012; 56: 176-183 [PMID: 21835141 DOI: 10.1016/j.jhep.2011.07.013]
38. Chresta CM, Davies BR, Hickson I, Harding T, Cosulich S, Critchlow SE, Vincent JP, Ellston R, Jones D, Sini P, James D, Howard Z, Dudley P, Hughes G, Smith L, Maguire S, Hummersone M, Malagu K, Menear K, Jenkins R, Jacobsen M, Smith GC, Guichard S, Pass M. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res 2010; 70: 288-298 [PMID: 20028854 DOI: 10.1158/0008-5472.CAN-09-1751]
39. Varga A, Mita MM, Wu J, Wu JJ, Nemunaitis JJ, Cloughesy TF, Mischel PS, Bendell JC, Shih KC, Paz-Ares LG, Mahipal A, Delord JP, Kelley RK, Soria JC, Wong L, Xu S, James A, Wu X, Chopra R, Hege K, Munster PN. Phase I expansion trial of an oral TORC1/TORC2 inhibitor (CC-223) in advanced solid tumors. Poster Presentation. Proc Am Soc Clin Onc 2013; 31: abstract 2606
40. Hughes LA, Melotte V, de Schrijver J, de Maat M, Smit VT, Bovée JV, French PJ, van den Brandt PA, Schouten LJ, de Meyer T, van Criekinge W, Ahuja N, Herman JG, Weijenberg MP, van Engeland M. The CpG island methylator phenotype: what's in a name? Cancer Res 2013; 73: 5858-5868 [PMID: 23801749 DOI: 10.1158/0008-5472.CAN-12-4306]
41. Data on file, Astex Pharmaceuticals, Inc.,. CA: Dublin, 2013