Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma

Clinical Cancer Research

Volumn 17, Issue 8, 2011, Pages 2373-2384

  Santiskulvong, Chintda ^a   Konecny, Gottfried E ^b   Fekete, Mirela ^a   Chen, Kuang Yui Michael ^a   Karam, Amer ^a   Mulholland, David ^b   Eng, Carol ^a   Wu, Hong ^b   Song, Min ^a   Dorigo, Oliver ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; ASPARTIC ACID; CASPASE 3; CISPLATIN; EVEROLIMUS; GLYCINE; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PLACEBO; PROTEIN KINASE B;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL; CANCER INHIBITION; CANCER MODEL; CANCER SURVIVAL; CELL MIGRATION; CELL PROLIFERATION; CHEMOSENSITIZATION; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG POTENTIATION; DRUG TARGETING; ENZYME ACTIVITY; FEMALE; GENE; GENE DELETION; GENE MUTATION; HUMAN; HUMAN CELL; IC 50; IN VIVO STUDY; MOUSE; NONHUMAN; ONCOGENE K RAS; OVARY CARCINOMA; PERITONEUM TUMOR; PRIORITY JOURNAL; PTEN GENE; SURVIVAL TIME; TISSUE SECTION;

ANIMALS; ANTINEOPLASTIC AGENTS; CASPASE 3; CELL CYCLE; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; CISPLATIN; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, NEOPLASM; ENZYME ACTIVATION; FEMALE; HUMANS; IMIDAZOLES; IMMUNOBLOTTING; MICE; MICE, TRANSGENIC; MUTATION; OVARIAN NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; QUINOLINES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 79954603804     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-10-2289     Document Type: Article

References (49)

1. Jemal A, Siegel R, Xu J, Ward E. Cancer Statistics, 2010. CA Cancer J Clin 2010;60:277-300.
2. Cannistra SA. Cancer of the ovary. N Engl J Med 2004;351:2519-29.
3. Martin VR. Ovarian cancer: an overview of treatment options. Clin J Oncol Nurs 2007;11:201-7.
4. Aletti GD, Gallenberg MM, Cliby WA, Jatoi A, Hartmann LC. Current management strategies for ovarian cancer. Mayo Clin Proc 2007;82:751-70. (Pubitemid 46878099)
5. Cheng JQ, Lindsley CW, Cheng GZ, Yang H, Nicosia SV. The Akt/PKB pathway: molecular target for cancer drug discovery. Oncogene 2005;24:7482-92. (Pubitemid 41637988)
6. Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 2006;6:184-92. (Pubitemid 43292562)
7. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489-501. (Pubitemid 37328931)
8. Altomare DA, Wang HQ, Skele KL, De Rienzo A, Klein-Szanto AJ, Godwin AK, et al. AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth. Oncogene 2004;23:5853-7. (Pubitemid 39093031)
9. Zhang L, Huang J, Yang N, Greshock J, Liang S, Hasegawa K, et al. Integrative genomic analysis of phosphatidylinositol 3'-kinase family identifies PIK3R3 as a potential therapeutic target in epithelial ovarian cancer. Clin Cancer Res 2007;13:5314-21. (Pubitemid 47510355)
10. Kurose K, Zhou XP, Araki T, Cannistra SA, Maher ER, Eng C. Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am J Pathol 2001;158:2097-106. (Pubitemid 32545195)
11. Shayesteh L, Lu Y, Kuo WL, Baldocchi R, Godfrey T, Collins C, et al. PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 1999;21:99-102. (Pubitemid 29036292)
12. Yuan ZQ, Sun M, Feldman RI, Wang G, Ma X, Jiang C, et al. Frequent activation of AKT2 and induction of apoptosis by inhibition of phosphoinositide-3-OH kinase/Akt pathway in human ovarian cancer. Oncogene 2000;19:2324-30. (Pubitemid 30307208)
13. Castellvi J, Garcia A, Rojo F, Ruiz-Marcellan C, Gil A, Baselga J, et al. Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer. Cancer 2006;107:1801-11. (Pubitemid 44582949)
14. Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther 2008;7:1851-63.
15. Roccaro AM, Sacco A, Husu EN, Pitsillides C, Vesole S, Azab AK, et al. Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy in Waldenstrom macroglobulinemia. Blood 2010;115:559-69.
16. Serra V, Markman B, Scaltriti M, Eichhorn PJ, Valero V, Guzman M, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res 2008;68:8022-30.
17. Liu TJ, Koul D, LaFortune T, Tiao N, Shen RJ, Maira SM, et al. NVPBEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas. Mol Cancer Ther 2009;8:2204-10.
18. McMillin DW, Ooi M, Delmore J, Negri J, Hayden P, Mitsiades N, et al. Antimyeloma activity of the orally bioavailable dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235. Cancer Res 2009;69:5835-42.
19. Marone R, Erhart D, Mertz AC, Bohnacker T, Schnell C, Cmiljanovic V, et al. Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors. Mol Cancer Res 2009;7:601-13.
20. Baumann P, Mandl-Weber S, Oduncu F, Schmidmaier R. The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma. Exp Cell Res 2008;5:485-97.
21. Konstantinidou G, Bey EA, Rabellino A, Schuster K, Maira MS, Gazdar AF, et al. Dual phosphoinositide 3-kinase/mammalian target of rapamycin blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS mutations. Cancer Res 2009;69:7644-52.
22. Faber AC, Li D, Song Y, Liang MC, Yeap BY, Bronson RT, et al. Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition. Proc Natl Acad Sci U S A 2009;106:19503-8.
23. Brachmann SM, Hofmann I, Schnell C, Fritsch C, Wee S, Lane H, et al. Specific apoptosis induction by the dual PI3K/mTor inhibitor NVPBEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells. Proc Natl Acad Sci U S A 2009;106:22299-304.
24. Nanni P, Nicoletti G, Landuzzi L, Croci S, Murgo A, Palladini A, et al. High metastatic efficiency of human sarcoma cells in Rag2/gammac double knockout mice provides a powerful test system for antimetastatic targeted therapy. Eur J Cancer 2010;46:659-68.
25. Manara MC, Nicoletti G, Zambelli D, Ventura S, Guerzoni C, Landuzzi L, et al. NVP-BEZ235 as a new therapeutic option for sarcomas. Clin Cancer Res 2010;16:530-40.
26. Bhatt AP, Bhende PM, Sin SH, Roy D, Dittmer DP, Damania B. Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas. Blood 2010;5:4455-63.
27. Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, García-Echeverría C, et al. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci U S A 2009;106:268-73.
28. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008;14:1351-6.
29. Ikediobi ON, Davies H, Bignell G, Edkins S, Stevens C, O'Meara S, et al. Mutation analysis of 24 known cancer genes in the NCI-60 cell line set. Mol Cancer Ther 2006;5:2606-12. (Pubitemid 44848987)
30. Saito M, Okamoto A, Kohno T, Takakura S, Shinozaki H, Isonishi S, et al. Allelic imbalance and mutations of the PTEN gene in ovarian cancer. Int J Cancer 2000;85:160-5. (Pubitemid 30023061)
31. Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 2005;11:63-70. (Pubitemid 40215839)
32. Fraser M, Leung BM, Yan X, Dan HC, Cheng JQ, Tsang BK. p53 is a determinant of X-linked inhibitor of apoptosis protein/Akt-mediated chemo-resistance in human ovarian cancer cells. Cancer Res 2003;63:7081-8. (Pubitemid 37413443)
33. Hu L, Hofmann J, Lu Y, Mills GB, Jaffe RB. Inhibition of phosphatidylinositol 3'-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. Cancer Res 2002;62:1087-92. (Pubitemid 34160292)
34. Hu L, Zaloudek C, Mills GB, Gray J, Jaffe RB. In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). Clin Cancer Res 2000;6:880-6. (Pubitemid 30159344)
35. Westfall SD, Skinner MK. Inhibition of phosphatidylinositol 3-kinase sensitizes ovarian cancer cells to carboplatin and allows adjunct chemotherapy treatment. Mol Cancer Ther 2005;4:1764-71. (Pubitemid 41685311)
36. Ohta T, Ohmichi M, Hayasaka T, Mabuchi S, Saitoh M, Kawagoe J, et al. Inhibition of phosphatidylinositol 3-kinase increases efficacy of cisplatin in in vivo ovarian cancer models. Endocrinology 2006;147:1761-9.
37. Mabuchi S, Altomare DA, Cheung M, Zhang L, Poulikakos PI, Hensley HH, et al. RAD001 inhibits human ovarian cancer cell proliferation, enhances cisplatin-induced apoptosis, and prolongs survival in an ovarian cancer model. Clin Cancer Res 2007;13:4261-70. (Pubitemid 47105991)
38. Mabuchi S, Altomare DA, Connolly DC, Klein-Szanto A, Litwin S, Hoelzle MK, et al. RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Res 2007;67:2408-13. (Pubitemid 46548923)
39. Mabuchi S, Ohmichi M, Kimura A, Hisamoto K, Hayakawa J, Nishio Y, et al. Inhibition of phosphorylation of BAD and Raf-1 by Akt sensitizes human ovarian cancer cells to paclitaxel. J Biol Chem 2002;277:33490-500. (Pubitemid 34984873)
40. Karam AK, Santiskulvong C, Fekete M, Zabih S, Eng C, Dorigo O. Cisplatin and PI3kinase inhibition decrease invasion and migration of human ovarian carcinoma cells and regulate matrix-metalloproteinase expression. Cytoskeleton (Hoboken) 2010;67:535-44.
41. Mabuchi S, Kawase C, Altomare DA, Morishige K, Sawada K, Hayashi M, et al. mTOR is a promising therapeutic target both in cisplatinsensitive and cisplatin-resistant clear cell carcinoma of the ovary. Clin Cancer Res 2009;15:5404-13.
42. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006;66:1500-8. (Pubitemid 43259931)
43. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, et al. Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 2005;65:7052-8. (Pubitemid 41161231)
44. Wan X, Harkavy B, Shen N, Grohar P, Helman LJ. Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Oncogene 2007;26:1932-40. (Pubitemid 46474636)
45. Schnell CR, Stauffer F, Allegrini PR, O'Reilly T, McSheehy PM, Dartois C, et al. Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging. Cancer Res 2008;68:6598-607.
46. Lee S, Choi EJ, Jin C, Kim DH. Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecol Oncol 2005;97:26-34. (Pubitemid 40403670)
47. Belyanskaya LL, Hopkins-Donaldson S, Kurtz S, Simões-Wüst AP, Yousefi S, Simon HU, et al. Cisplatin activates Akt in small cell lung cancer cells and attenuates apoptosis by survivin upregulation. Int J Cancer 2005;117:755-63. (Pubitemid 41598826)
48. Winograd-Katz SE, Levitzki A. Cisplatin induces PKB/Akt activation and p38 (MAPK) phosphorylation of the EGF receptor. Oncogene 2006;25:7381-90. (Pubitemid 44853429)
49. Dowling RJ, Topisirovic I, Alain T, Bidinosti M, Fonseca BD, Petroulakis E, et al. mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science 2010;328:1172-6.