Preclinical evaluation of combined TKI-258 and RAD001 in hepatocellular carcinoma

Cancer Chemotherapy and Pharmacology

Volumn 71, Issue 6, 2013, Pages 1417-1425

  Chan, Stephen L ^a   Wong, Chi Hang ^a   Lau, Cecilia P Y ^a   Zhou, Qian ^a   Hui, Connie W C ^a   Lui, Vivian W Y ^b   Ma, Brigette B Y ^a   Chan, Anthony T C ^a   Yeo, Winnie ^a  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

AKT; Hepatocellular carcinoma; mTOR; RAD001; TKI 258

Indexed keywords

CELL PROTEIN; DOVITINIB; EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; MITOGEN ACTIVATED PROTEIN KINASE P38; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PROCASPASE 3; PROTEIN KINASE B; PROTEIN PI 4EBP1; PROTEIN PI P70S6K; PROTEIN PI S6; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CANCER INHIBITION; CAPILLARY DENSITY; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IC 50; LIVER CELL CARCINOMA; MALE; MONOTHERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; BENZIMIDAZOLES; BLOTTING, WESTERN; CARCINOMA, HEPATOCELLULAR; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; HUMANS; LIVER NEOPLASMS; MICE; MICE, NUDE; NEOVASCULARIZATION, PATHOLOGIC; PROTO-ONCOGENE PROTEINS C-AKT; QUINOLONES; SIROLIMUS; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84878635090     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-013-2139-4     Document Type: Article

References (26)

1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74-108
2. Chan SL, Yeo W (2012) Targeted therapy of hepatocellular carcinoma: present and future. J Gastroenterol Hepatol 27(5):862-872. doi: 10.1111/j.1440-1746.2012.07096.x
3. Chan SL, Mo FK, Johnson PJ, Liem GS, Chan TC, Poon MC, Ma BB, Leung TW, Lai PB, Chan AT, Mok TS, Yeo W (2011) Prospective validation of the Chinese University Prognostic Index and comparison with other staging systems for hepatocellular carcinoma in an Asian population. J Gastroenterol Hepatol 26(2):340-347. doi: 10.1111/j.1440-1746.2010.06329.x
4. 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, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378-390
5. Villanueva A, Chiang DY, Newell P, Peix J, Thung S, Alsinet C, Tovar V, Roayaie S, Minguez B, Sole M, Battiston C, Van Laarhoven S, Fiel MI, Di Feo A, Hoshida Y, Yea S, Toffanin S, Ramos A, Martignetti JA, Mazzaferro V, Bruix J, Waxman S, Schwartz M, Meyerson M, Friedman SL, Llovet JM (2008) Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 135(6):1972-1983, 1983 e1971-e1911. doi: 10.1053/j.gastro.2008.08.008
6. Sahin F, Kannangai R, Adegbola O, Wang J, Su G, Torbenson M (2004) mTOR and P70 S6 kinase expression in primary liver neoplasms. Clin Cancer Res 10(24):8421-8425. doi: 10.1158/1078-0432.CCR-04-0941
7. Huynh H, Chow KH, Soo KC, Toh HC, Choo SP, Foo KF, Poon D, Ngo VC, Tran E (2009) RAD001 (everolimus) inhibits tumour growth in xenograft models of human hepatocellular carcinoma. J Cell Mol Med 13(7):1371-1380. doi: 10.1111/j.1582-4934.2008.00364.x
8. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N (2006) mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66(3):1500-1508
9. Zhou Q, Lui VW, Lau CP, Cheng SH, Ng MH, Cai Y, Chan SL, Yeo W (2012) Sustained antitumor activity by co-targeting mTOR and the microtubule with temsirolimus/vinblastine combination in hepatocellular carcinoma. Biochem Pharmacol 83(9):1146-1158. doi: 10.1016/j.bcp.2012.01.013
10. Wu X, Ge H, Lemon B, Vonderfecht S, Weiszmann J, Hecht R, Gupte J, Hager T, Wang Z, Lindberg R, Li Y (2010) FGF19-induced hepatocyte proliferation is mediated through FGFR4 activation. J Biol Chem 285(8):5165-5170. doi: 10.1074/jbc.M109.068783
11. Lee SH, Lopes de Menezes D, Vora J, Harris A, Ye H, Nordahl L, Garrett E, Samara E, Aukerman SL, Gelb AB, Heise C (2005) In vivo target modulation and biological activity of CHIR-258, a multitargeted growth factor receptor kinase inhibitor, in colon cancer models. Clin Cancer Res 11(10):3633-3641. doi: 10.1158/1078-0432.CCR-04-2129
12. Renhowe PA, Pecchi S, Shafer CM, Machajewski TD, Jazan EM, Taylor C, Antonios-McCrea W, McBride CM, Frazier K, Wiesmann M, Lapointe GR, Feucht PH, Warne RL, Heise CC, Menezes D, Aardalen K, Ye H, He M, Le V, Vora J, Jansen JM, Wernette-Hammond ME, Harris AL (2009) Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine kinase inhibitors. J Med Chem 52(2):278-292. doi: 10.1021/jm800790t
13. Trudel S, Li ZH, Wei E, Wiesmann M, Chang H, Chen C, Reece D, Heise C, Stewart AK (2005) CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood 105(7):2941-2948. doi: 10.1182/blood-2004-10-3913
14. Lopes de Menezes DE, Peng J, Garrett EN, Louie SG, Lee SH, Wiesmann M, Tang Y, Shephard L, Goldbeck C, Oei Y, Ye H, Aukerman SL, Heise C (2005) CHIR-258: a potent inhibitor of FLT3 kinase in experimental tumor xenograft models of human acute myelogenous leukemia. Clin Cancer Res 11(14):5281-5291. doi: 10.1158/1078-0432.CCR-05-0358
15. Sarker D, Molife R, Evans TR, Hardie M, Marriott C, Butzberger-Zimmerli P, Morrison R, Fox JA, Heise C, Louie S, Aziz N, Garzon F, Michelson G, Judson IR, Jadayel D, Braendle E, de Bono JS (2008) A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin Cancer Res 14(7):2075-2081. doi: 10.1158/1078-0432.CCR-07-1466
16. Huynh H, Chow PK, Tai WM, Choo SP, Chung AY, Ong HS, Soo KC, Ong R, Linnartz R, Shi MM (2012) Dovitinib demonstrates antitumor and antimetastatic activities in xenograft models of hepatocellular carcinoma. J Hepatol 56(3):595-601. doi: 10.1016/j.jhep.2011.09.017
17. Tai WT, Cheng AL, Shiau CW, Liu CY, Ko CH, Lin MW, Chen PJ, Chen KF (2012) Dovitinib induces apoptosis and overcomes sorafenib resistance in hepatocellular carcinoma through SHP-1-mediated inhibition of STAT3. Mol Cancer Ther 11(2):452-463. doi: 10.1158/1535-7163.MCT-11-0412
18. Abou-Alfa GK, Johnson P, Knox JJ, Capanu M, Davidenko I, Lacava J, Leung T, Gansukh B, Saltz LB (2010) Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA 304(19):2154-2160. doi: 10.1001/jama.2010.1672
19. Abou-Alfa GK, Chan SL, Lin CC, Chiorean EG, Holcombe RF, Mulcahy MF, Carter WD, Patel K, Wilson WR, Melink TJ, Gutheil JC, Tsao CJ (2011) PR-104 plus sorafenib in patients with advanced hepatocellular carcinoma. Cancer Chemother Pharmacol 68(2):539-545. doi: 10.1007/s00280-011-1671-3
20. Chan SL, Mok T, Ma BB (2012) Management of hepatocellular carcinoma: beyond sorafenib. Curr Oncol Rep. doi: 10.1007/s11912-012-0233-0
21. 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 (2009) 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 10(1):25-34
22. El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132(7):2557-2576
23. Ma BB, Lui VW, Hui EP, Lau CP, Ho K, Ng MH, Cheng SH, Tsao SW, Chan AT (2010) The activity of mTOR inhibitor RAD001 (everolimus) in nasopharyngeal carcinoma and cisplatin-resistant cell lines. Invest New Drugs 28(4):413-420. doi: 10.1007/s10637-009-9269-x
24. Dey JH, Bianchi F, Voshol J, Bonenfant D, Oakeley EJ, Hynes NE (2010) Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis. Cancer Res 70(10):4151-4162. doi: 10.1158/0008-5472.CAN-09-4479
25. Breuleux M, Klopfenstein M, Stephan C, Doughty CA, Barys L, Maira SM, Kwiatkowski D, Lane HA (2009) Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition. Mol Cancer Ther 8(4):742-753. doi: 10.1158/1535-7163.MCT- 08-0668
26. Zhou Q, Wong CH, Lau CPY, Hui CWC, Lui VW, Chan SL, Yeo W (2013) Enhanced antitumor activity with combining effect of mTOR inhibition and in microtubule-stabilization in hepatocellular carcinoma. Int J Hepatol 2013:103830. doi: 10.1155/2013/103830