Potential role of mTORC2 as a therapeutic target in clear cell carcinoma of the ovary

Molecular Cancer Therapeutics

Volumn 12, Issue 7, 2013, Pages 1367-1377

  Hisamatsu, Takeshi ^a   Mabuchi, Seiji ^a   Matsumoto, Yuri ^a   Kawano, Mahiru ^a   Sasano, Tomoyuki ^a   Takahashi, Ryoko ^a   Sawada, Kenjiro ^a   Ito, Kimihiko ^b   Kurachi, Hirohisa ^c   Schilder, Russell J ^d   Testa, Joseph R ^e   Kimura, Tadashi ^a  

^a OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b KANSAI ROSAI HOSPITAL   (Japan)

^c YAMAGATA UNIVERSITY   (Japan)

^d THOMAS JEFFERSON UNIVERSITY   (United States)

^e FOX CHASE CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AZD 8055; EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PROLINE RICH AKT SUBSTRATE 40; PROTEIN; PROTEIN KINASE B; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER RESISTANCE; CLEAR CELL CARCINOMA; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENTIATION; DRUG SENSITIVITY; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; FEMALE; HISTOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; MOUSE; NONHUMAN; OVARY CARCINOMA; PRIMARY TUMOR; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TISSUE MICROARRAY; WESTERN BLOTTING;

EID: 84880076309     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-12-1185     Document Type: Article

References (39)

1. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012;149:274-93.
2. Wander SA, Hennessy BT, Slingerland JM. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy. J Clin Invest 2011;121:1231-41.
3. 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)
4. Mabuchi S, Kawase C, Altomare DA, Morishige K, Sawada K, Hayashi M, et al. mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary. Clin Cancer Res 2009;15:5404-13.
5. Kuo KT, Mao TL, Jones S, Veras E, Ayhan A, Wang TL, et al. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol 2009;174:1597-601.
6. Mabuchi S, Hisamatsu T, Kimura T. Targeting mTOR signaling pathway in ovarian cancer. Curr Med Chem 2011;18:2960-8.
7. NCT 01196429. ClinicalTrials.gov. A service of the U.S. National Institute of Health. http://www.clinicaltrials.gov (accessed May 15, 2013).
8. Winter WE III, Maxwell GL, Tian C, Carlson JW, Ozols RF, Rose PG, et al. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2007;25:3621-7. (Pubitemid 47372600)
9. Crotzer DR, Sun CC, Coleman RL, Wolf JK, Levenback CF, Gershenson DM. Lack of effective systemic therapy for recurrent clear cell carcinoma of the ovary. Gynecol Oncol 2007;105:404-8. (Pubitemid 46590333)
10. Del Carmen MG, Birrer M, Schorge JO. Clear cell carcinoma of the ovary: a review of the literature. Gynecol Oncol 2012;126:481-90.
11. Sabatini DM, mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 2006;6:729-34. (Pubitemid 44286004)
12. Bhagwat SV, Crew AP. Novel inhibitors of mTORC1 and mTORC2. Curr Opin Investig Drugs 2010;11:638-45.
13. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449-56.
14. Mabuchi S, Hisamatsu T, Kawase C, Hayashi M, Sawada K, Mimura K, et al. The activity of trabectedin as a single agent or in combination with everolimus for clear cell carcinoma of the ovary. Clin Cancer Res 2011;17:4462-73.
15. 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)
16. 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)
17. Miyazawa M, Yasuda M, Fujita M, Kajiwara H, Hirabayashi K, Takekoshi S, et al. Therapeutic strategy targeting the mTOR-HIF-1alpha-VEGF pathway in ovarian clear cell adenocarcinoma. Pathol Int 2009;59:19-27.
18. Montero JC, Chen X, Ocaña A, Pandiella A. Predominance of mTORC1 over mTORC2 in the regulation of proliferation of ovarian cancer cells: therapeutic implications. Mol Cancer Ther 2012;11:1342-52.
19. Nozawa S, Tsukazaki K, Sakayori M, Jeng CH, Iizuka R. Establishment of a human ovarian clear cell carcinoma cell line (RMG-I) and its single cell cloning-with special reference to the stem cell of the tumor. Hum Cell 1988;1:426-35.
20. Nozawa S, Yajima M, Sasaki H, Tsukazaki K, Aoki D, Sakayori M, et al. A new CA125-like antigen (CA602) recognized by two monoclonal antibodies against a newly established ovarian clear cell carcinoma cell line (RMG-II). Jpn J Cancer Res 1991;82:854-61.
21. Tomioka Y. Establishment and characterization of three human ovarian clear cell carcinoma cell line. J Kurume Med Assoc 1998;61:323-33.
22. Takemoto Y, Yano H, Momosaki S, Ogasawara S, Nishida N, Kojiro S, et al. Antiproliferative effects of interferon-alphaCon1 on ovarian clear cell adenocarcinoma in vitro and in vivo. Clin Cancer Res 2004;10:7418-26. (Pubitemid 39487731)
23. Niimi S, Nakagawa K, Sugimoto Y, Nishio K, Fujiwara Y, Yokoyama S, et al. Mechanism of cross-resistance to a camptothecin analogue (CPT-11) in a human ovarian cancer cell line selected by cisplatin. Cancer Res 1992;52:328-33.
24. Mabuchi S, Kawase C, Altomare DA, Morishige K, Hayashi M, Sawada K, et al. Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary. Mol Cancer Ther 2010;9:2411-22.
25. Mabuchi S, Ohmichi M, Nishio Y, Hayasaka T, Kimura A, Ohta T, et al. Inhibition of NFkappaB increases the efficacy of cisplatin in in vitro and in vivo ovarian cancer models. J Biol Chem 2004;279:23477-85. (Pubitemid 38685659)
26. Huang J. An in vitro assay for the kinase activity of mTOR complex 2. Methods Mol Biol 2012;821:75-86.
27. Copp J, Manning G, Hunter T. TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. Cancer Res 2009;69:1821-7.
28. Carayol N, Vakana E, Sassano A, Kaur S, Goussetis DJ, Glaser H, et al. Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells. Proc Natl Acad Sci U S A 2010;107:12469-74.
29. Proud CG. mTORC1 signalling and mRNA translation. Biochem Soc Trans 2009;37:227-31.
30. Wang H, Zhang Q, Wen Q, Zheng Y, Philip L, Jiang H, et al. Proline-rich Akt substrate of 40kDa (PRAS40): a novel downstream target of PI3k/Akt signaling pathway. Cell Signal 2012;24:17-24.
31. Gupta M, Ansell SM, Novak AJ, Kumar S, Kaufmann SH, Witzig TE. Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell lymphoma by inhibiting Akt signaling through mTORC2. Blood 2009;114:2926-35.
32. Dibble CC, Asara JM, Manning BD. Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol 2009;29:5657-70.
33. Sugiyama T, Kamura T, Kigawa J, Terakawa N, Kikuchi Y, Kita T, et al. Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer 2000;88:2584-9. (Pubitemid 30331967)
34. Behbakht K, Sill MW, Darcy KM, Rubin SC, Mannel RS, Waggoner S, et al. Phase II trial of themTORinhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study. Gynecol Oncol 2011;123:19-26.
35. Hietakangas V, Cohen SM. TOR complex 2 is needed for cell cycle progression and anchorage-independent growth of MCF7 and PC3 tumor cells. BMC Cancer 2008;8:282.
36. Bashir T, Cloninger C, Artinian N, Anderson L, Bernath A, Holmes B, et al. Conditional astroglial Rictor overexpression induces malignant glioma in mice. PLoS ONE 2012;7:e47741.
37. Chresta CM, Davies BR, Hickson I, Harding T, Cosulich S, Critchlow SE, et al. 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;70:288-98.
38. Shi Y, Yan H, Frost P, Gera J, Lichtenstein A. Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade. Mol Cancer Ther 2005;4:1533-40. (Pubitemid 41556435)
39. Cloughesy TF, Yoshimoto K, Nghiemphu P, Brown K, Dang J, Zhu S, et al. Antitumor activity of rapamycin in a phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med 2008;5:e8. Technology Technology