In vivo antitumor effect of the mTOR inhibitor CCI-779 and gemcitabine in xenograft models of human pancreatic cancer

International Journal of Cancer

Volumn 118, Issue 9, 2006, Pages 2337-2343

  Ito, Daisuke ^a   Fujimoto, Koji ^a   Mori, Tomohiko ^a   Kami, Kazuhiro ^a   Koizumi, Masayuki ^a   Toyoda, Eiji ^a   Kawaguchi, Yoshiya ^a   Doi, Ryuichiro ^a  

^a KYOTO UNIVERSITY   (Japan)

Author keywords

CCI 779; mTOR; Pancreatic cancer

Indexed keywords

GEMCITABINE; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B BETA; S6 KINASE; TEMSIROLIMUS;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; CANCER PATIENT; CANCER SURVIVAL; CELL CYCLE G1 PHASE; CELL GROWTH; CELL PROLIFERATION; EFFECTOR CELL; HUMAN; HUMAN CELL; MAMMAL CELL; MITOGENESIS; PANCREAS ADENOCARCINOMA; PRIORITY JOURNAL; PROTEIN SYNTHESIS REGULATION; TUMOR XENOGRAFT;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ADENOCARCINOMA; ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; CARCINOMA, PANCREATIC DUCTAL; DEOXYCYTIDINE; FEMALE; HUMANS; MICE; MICE, NUDE; PANCREATIC NEOPLASMS; PROTEIN KINASES; SIGNAL TRANSDUCTION; SIROLIMUS; SURVIVAL ANALYSIS; TRANSPLANTATION, HETEROLOGOUS;

EID: 33645690146     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.21532     Document Type: Article

References (43)

1. Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin 2001;51:15-36.
2. Rosewicz S, Wiedenmann B. Pancreatic carcinoma. Lancet 1997;349:485-9.
3. Burris HA, III, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15:2403-13.
4. Goldstein LJ, Galski H, Fojo A, Willingham M, Lai SL, Gazdar A, Pirker R, Green A, Crist W, Brodeur GM, Lieber M, Cossman J, et al. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 1989;81:116-24.
5. Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000;103:253-62.
6. Riesterer O, Zingg D, Hummerjohann J, Bodis S, Pruschy M. Degradation of PKB/Akt protein by inhibition of the VEGF receptor/mTOR pathway in endothelial cells. Oncogene 2004;23:4624-35.
7. Krasilnikov MA. PhosphatidyIinositol-3 kinase dependent pathways: the role in control of cell growth, survival, and malignant transformation. Biochemistry (Moscow) 2000;65:59-67.
8. Bondar VM, Sweeney-Gotsch B, Andreeff M, Mills GB, MeConkey DJ. Inhibition of the phosphatidylinositol 3′-kinase-AKT pathway induces apoptosis in pancreatic carcinoma cells in vitro and in vivo. Mol Cancer Ther 2002;1:989-97.
9. Akselband Y, Harding MW, Nelson PA. Rapamycin inhibits spontaneous and fibroblast growth factor β-stimulated proliferation of endothelial cells and fibroblasts. Transplant Proc 1991;23:2833-6.
10. Francavilla A, Starzl TE, Carr B, Azzarone A, Carrieri G, Zeng QH, Porter KA. The effects of FK 506, cyclosporine, and rapamycin on liver growth in vitro and in vivo. Transplant Proc 1991;23:2817-20.
11. Albers MW, Williams RT, Brown EJ, Tanaka A, Hall FL, Schreiber SL. FKBP-rapamycin inhibits a cyclin-dependent kinase activity and a cyclin D1-Cdk association in early G1 of an osteosarcoma cell line. J Biol Chem 1993;268:22825-9.
12. Jayaraman T, Marks AR. Rapamycin-FKBP12 blocks proliferation, induces differentiation, and inhibits cdc2 kinase activity in a myogenic cell line. J Biol Chem 1993;268:25385-8.
13. Dilling MB, Dias P, Shapiro DN, Germain GS, Johnson RK, Houghton PJ. Rapamycin selectively inhibits the growth of childhood rhabdomyosarcoma cells through inhibition of signaling via the type I insulin-like growth factor receptor. Cancer Res 1994;54:903-7.
14. Marx SO, Jayaraman T, Go LO, Marks AR. Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. Circ Res 1995;76:412-7.
15. Hu L, Shi Y, Hsu JH, Gera J, Van Ness B, Lichienstein A. Down-stream effectors of oncogenic ras in multiple myeloma cells. Blood 2003;101:3126-35.
16. Huang S, Houghton PJ. Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol 2003;3:371-7.
17. Mita MM, Mita A, Rowinsky EK. Mammalian target of rapamycin: a new molecular target for breast cancer. Clin Breast Cancer 2003;4:126-37.
18. Panwalkar A, Verstovsek S, Giles FJ. Mammalian target of rapamycin inhibition as therapy for hematologic malignancies. Cancer 2004;100:657-66.
19. Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK, Testa JR. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci USA 1996;93:3636-41.
20. Ruggeri BA, Huang L, Wood M, Cheng JQ, Testa JR. Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol Carcinog 1998;21:81-6.
21. Altomare DA, Tanno S, De Rienzo A, Klein-Szanto AJ, Skele KL, Hoffman JP, Testa JR. Frequent activation of AKT2 kinase in human pancreatic carcinomas. J Cell Biochem 2003;88:470-6.
22. Grewe M, Gansauge F, Schmid RM, Adler G, Seufferlein T. Regulation of cell growth and cyclin D1 expression by the constitutively active FRAP-p70s6K pathway in human pancreatic cancer cells. Cancer Res 1999;59:3581-7.
23. Shah SA, Potter MW, Ricciardi R, Perugini RA, Gallery MP. FRAP-p70s6K signaling is required for pancreatic cancer cell proliferation. J Sure Res 2001;97:123-30.
24. Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR, Park Y, Liou SH, Marshall B, Boni JP, Dukart G, Sherman ML. Randomized phase 11 study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 2004;22:909-18.
25. Frost P, Moatamed F, Hoang B, Shi Y, Gera J, Yan H, Gibbons J, Lichtenstein A. In vivo anlitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model. Blood 2004;104:4181-7.
26. Kato M, Shimada Y, Tanaka H, Hosotani R, Ohshio G, Ishizaki K, Imamura M. Characterization of six cell lines established from human pancreatic adenocarcinomas. Cancer 1999;85:832-40.
27. Fujimoto K, Sheng H, Shao J, Beauchamp RD. Transforming growth factor-β1 promotes invasiveness after cellular transformation with activated Ras in intestinal epithelial cells. Exp Cell Res 2001;266:239-49.
28. Matsumoto J, Kaneda M, Tada M, Hamada J, Okushiba S, Kondo S, Katoh H, Moriuchi T. Differential mechanisms of constitutive Akt/PKB activation and its influence on gene expression in pancreatic cancer cells. Jpn J Cancer Res 2002;93:1317-26.
29. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004;363:1049-57.
30. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003;3:11-22.
31. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489-501.
32. Gera JF, Mellinghoff IK, Shi Y, Rettig MB, Tran C, Hsu JH, Sawyers CL, Lichtenstein AK. AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression. J Biol Chem 2004;279:2737-46.
33. Neshat MS, Mellinghoff IK, Tran C, Stiles B, Thomas G, Petersen R. Frost P, Gibbons JJ, Wu H, Sawyers CL. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci USA 2001;98:10314-9.
34. Podsypanina K, Lee RT, Politis C, Hennessy I, Crane A, Puc J, Neshat M, Wang H, Yang L, Gibbons J, Frost P, Dreisbach V, et al. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc Natl Acad Sci USA 2001;98:10320-5.
35. McMenamin ME, Soung P, Perera S, Kaplan I, Locla M, Sellers WR. Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res 1999;59:4291-6.
36. Sakurada A, Suzuki A, Sato M, Yamakawa H, Orikasa K, Uyeno S, Ono T, Ohuchi N, Fujimura S, Horii A. Infrequent genetic alterations of the PTEN/MMACI gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary. Jpn J Cancer Res 1997;88:1025-8.
37. Peralba JM, DeGraffenried L, Friedrichs W, Fulcher L, Grunwald V, Weiss G, Hidalgo M. Pharmacodynamic Evaluation of CCI-779, an Inhibitor of mTOR, in Cancer Patients. Clin Cancer Res 2003;9:2887-92.
38. Noh WC, Mondesire WH, Peng J, Jian W, Zhang H, Dong J, Mills GB, Hung MC, Meric-Bernstam F. Determinants of rapamycin sensitivity in breast cancer cells. Clin Cancer Res 2004;10:1013-23.
39. Stephan S, Datta K, Wang E, Li J, Brekken RA, Parangi S, Thorpe PE, Mukhopadhyay D. Effect of rapamycin alone and in combination with antiangiogenesis therapy in an orthotopic model of human pancreatic cancer. Clin Cancer Res 2004;10:6993-7000.
40. Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C, Farkas S, Anthuber M, Jauch KW, Geissler EK. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial crowth factor. Nat Med 2002;8:128-35.
41. El-Hashemite N, Walker V, Zhang H, Kwiatkowski DJ. Loss of Tsc1 or Tsc2 induces vascular endothelial growth factor production through mammalian target of rapamycin. Cancer Res 2003;63:5173-7.
42. Fujimoto K, Hosotani R, Wada M, Lee JU, Koshiba T, Miyamoto Y, Tsuji S, Nakajima S, Doi R, Imamura M. Expression of two angiogenic factors, vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relationship to angiogenesis. Eur J Cancer 1998;34:1439-47.
43. Bruns CJ, Koehl GE, Guba M, Yezhelyev M, Steinbauer M, Seeliger H, Schwend A, Hoehn A, Jauch KW, Geissler EK. Rapamycin-induced endothelial cell death and tumor vessel thrombosis potentiate cytotoxic therapy against pancreatic cancer. Clin Cancer Res 2004;10:2109-19.