Everolimus augments the effects of sorafenib in a syngeneic orthotopic model of hepatocellular carcinoma

Molecular Cancer Therapeutics

Volumn 10, Issue 6, 2011, Pages 1007-1017

  Piguet, Anne Christine ^a   Saar, Bettina ^b   Hlushchuk, Ruslan ^c   St Pierre, Marie V ^a   McSheehy, Paul M J ^d   Radojevic, Vesna ^a   Afthinos, Maresa ^a   Terracciano, Luigi ^e   Djonov, Valentin ^c   Dufour, Jean Fraņcois ^a,b  

^a UNIVERSITY OF BERN   (Switzerland)

^b UNIVERSITY OF BERN   (Switzerland)

^c UNIVERSITY OF FRIBOURG   (Switzerland)

^d NOVARTIS PHARMA AG   (Switzerland)

^e UNIVERSITY HOSPITAL BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

EVEROLIMUS; MESSENGER RNA; SORAFENIB; UVOMORULIN; VASCULOTROPIN A;

ADD ON THERAPY; ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER SURVIVAL; CONTROLLED STUDY; DRUG DOSE SEQUENCE; DRUG TOLERABILITY; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL CARCINOMA; LIVER NECROSIS; MALE; MONOTHERAPY; MORRIS HEPATOMA; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RAT; TOOTH FRACTURE; TUMOR VOLUME; VASCULAR RING;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BENZENESULFONATES; CARRIER PROTEINS; CELL PROLIFERATION; DRUG SYNERGISM; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; LIVER NEOPLASMS, EXPERIMENTAL; MALE; MITOGEN-ACTIVATED PROTEIN KINASE 3; NEOVASCULARIZATION, PATHOLOGIC; PHOSPHOPROTEINS; PYRIDINES; RANDOM ALLOCATION; RATS; SIROLIMUS; TUMOR BURDEN; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 79958742182     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-10-0666     Document Type: Article

References (32)

1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90.
2. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. 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.
3. Calvisi DF, Ladu S, Gorden A, Farina M, Conner EA, Lee JS, et al. Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 2006;130:1117-28.
4. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004;64:7099-109. (Pubitemid 39331023)
5. Whittaker S, Marais R, Zhu AX. The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene 2010;29:4989-5005.
6. Semela D, Piguet AC, Kolev M, Schmitter K, Hlushchuk R, Djonov V, et al. Vascular remodeling and antitumoral effects of mTOR inhibition in a rat model of hepatocellular carcinoma. J Hepatol 2007;46:840-8. (Pubitemid 46529039)
7. Huynh H, Ngo VC, Koong HN, Poon D, Choo SP, Thng CH, et al. Sorafenib and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma. J Cell Mol Med 2009;13:2673-83.
8. Yang R, Rescorla FJ, Reilly CR, Faught PR, Sanghvi NT, Lumeng L, et al. A reproducible rat liver cancer model for experimental therapy: introducing a technique of intrahepatic tumor implantation. J Surg Res 1992;52:193-8.
9. Djonov VG, Kurz H, Burri PH. Optimality in the developing vascular system: branching remodeling by means of intussusception as an efficient adaptation mechanism. Dev Dyn 2002;224:391-402. (Pubitemid 34848063)
10. Lowry O, Rosebrough N, Farr L, Randall R. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265-75.
11. Sieghart W, Fuereder T, Schmid K, Cejka D, Werzowa J, Wrba F, et al. Mammalian target of rapamycin pathway activity in hepatocellular carcinomas of patients undergoing liver transplantation. Transplantation 2007;83:425-32. (Pubitemid 46667846)
12. Villanueva A, Chiang DY, Newell P, Peix J, Thung S, Alsinet C, et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008;135:1972-1983, 1983.e1-11.
13. Boyault S, Rickman DS, de Reynies A, Balabaud C, Rebouissou S, Jeannot E, et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology 2007;45:42-52. (Pubitemid 46144363)
14. Newell P, Toffanin S, Villanueva A, Chiang DY, Minguez B, Cabellos L, et al. Ras pathway activation in hepatocellular carcinoma and antitumoral effect of combined sorafenib and rapamycin in vivo. J Hepatol 2009;51:725-33.
15. Wang Z, Zhou J, Fan J, Qiu SJ, Yu Y, Huang XW, et al. Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res 2008;14:5124-30.
16. Semela D, Dufour JF. Angiogenesis and hepatocellular carcinoma. J Hepatol 2004;41:864-80. (Pubitemid 39434320)
17. Drevs J. Soluble markers for the detection of hypoxia under anti-angiogenic treatment. Anticancer Res 2003;23:1159-61. (Pubitemid 36750934)
18. Zhu AX, Sahani DV, Duda DG, di Tomaso E, Ancukiewicz M, Catalano OA, et al. Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol 2009;27:3027-35.
19. Saranadasa M, Wang ES. Vascular endothelial growth factor inhibition: conflicting roles in tumor growth. Cytokine 2011;53:115-29.
20. Lane HA, Wood JM, McSheehy PM, Allegrini PR, Boulay A, Brueggen J, et al. mTOR inhibitor RAD001 (everolimus) has antiangiogenic/ vascular properties distinct from a VEGFR tyrosine kinase inhibitor. Clin Cancer Res 2009;15:1612-22.
21. 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.
22. Di Nicolantonio F, Arena S, Tabernero J, Grosso S, Molinari F, Macarulla T, et al. Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus. J Clin Invest 2010;120:2858-66.
23. Hosoi H, Dilling MB, Liu LN, Danks MK, Shikata T, Sekulic A, et al. Studies on the mechanism of resistance to rapamycin in human cancer cells. Mol Pharmacol 1998;54:815-24. (Pubitemid 28523173)
24. Cote GJ, Lastra BA, Cook JR, Huang DP, Chiu JF. Oncogene expression in rat hepatomas and during hepatocarcinogenesis. Cancer Lett 1985;26:121-7. (Pubitemid 15139649)
25. Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM, Lynch M. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 2008;7:3129-40.
26. Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA, Dixit V, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 30-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 1998;273:30336-43. (Pubitemid 28545503)
27. Fuereder T, Jaeger-Lansky A, Hoeflmayer D, Preusser M, Strommer S, Cejka D, et al. mTOR inhibition by everolimus counteracts VEGF induction by sunitinib and improves anti-tumor activity against gastric cancer in vivo. Cancer Lett 2010;296:249-56.
28. Breuleux M, Klopfenstein M, Stephan C, Doughty CA, Barys L, Maira SM, et al. 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.
29. Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest 2008;118:3065-74.
30. Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009;15:220-31.
31. Moon KC, Cho SY, Lee HS, Jeon YK, Chung JH, Jung KC, et al. Distinct expression patterns of E-cadherin and beta-catenin in signet ring cell carcinoma components of primary pulmonary adenocarcinoma. Arch Pathol Lab Med 2006;130:1320-25. (Pubitemid 44373068)
32. Ebos JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009;15:232-9.