Novel phosphoinositide 3-kinase/mTOR dual inhibitor, NVP-BGT226, displays potent growth-inhibitory activity against human head and neck cancer cells in vitro and in vivo

Clinical Cancer Research

Volumn 17, Issue 22, 2011, Pages 7116-7126

  Chang, Kwang Yu ^a,b,c   Tsai, Shan Yin ^d   Wu, Ching Ming ^a   Yen, Chia Jui ^a,c   Chuang, Bin Fay ^b   Chang, Jang Yang ^b,c  

^a NATIONAL CHENG KUNG UNIVERSITY   (Taiwan)

^b NATIONAL HEALTH RESEARCH INSTITUTES   (Taiwan)

^c NATIONAL CHENG KUNG UNIVERSITY HOSPITAL   (Taiwan)

^d KAOHSIUNG MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; 3 METHYLADENINE; 8 (6 METHOXY PYRIDIN 3 YL) 3 METHYL 1 (4 PIPERAZIN 1 YL 3 TRIFLUOROMETHYL PHENYL) 1,3 DIHYDROIMIDAZO[4,5 C]QUINOLIN 2 ONE MALEATE; BECLIN 1; CASPASE 3; CASPASE 7; CISPLATIN; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MICROTUBULE ASSOCIATED PROTEIN; MICROTUBULE ASSOCIATED PROTEIN LIGHT CHAIN 3B II; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NVP BGT 226; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B; PROTEIN P62; RAPAMYCIN; S6 KINASE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CANCER CELL CULTURE; CANCER INHIBITION; CANCER RESISTANCE; CANCER SIZE; CELL CYCLE ARREST; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; CELL SURVIVAL; CONCENTRATION RESPONSE; CONTROLLED STUDY; CROSS RESISTANCE; CYTOPLASM; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG POTENCY; ENZYME ACTIVATION; ENZYME ANALYSIS; FLOW CYTOMETRY; GENE SILENCING; GROWTH INHIBITION; HEAD AND NECK CANCER; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NICK END LABELING; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TREATMENT DURATION; TUMOR XENOGRAFT; UPREGULATION;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG EVALUATION, PRECLINICAL; HEAD AND NECK NEOPLASMS; HUMANS; IMIDAZOLES; MALE; MICE; MICE, NUDE; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; QUINOLINES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 81255129000     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-11-0796     Document Type: Article

References (46)

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002.CA Cancer J Clin 2005;55:74-108. (Pubitemid 40372904)
2. DepartmentofHealth.Cancerregistryannual reportinTaiwanarea,2006. Taipei (Taiwan): Department of Health, The Executive Yuan, ROC; 2009.
3. Ko YC, Huang YL, Lee CH, Chen MJ, Lin LM, Tsai CC. Betel quid chewing, cigarette smoking, and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med 1995;24:450-3.
4. Wong LY, Wei WI, Lam LK, Yuen AP. Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery. Head Neck 2003;25:953-9. (Pubitemid 37323011)
5. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78. (Pubitemid 43209104)
6. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-27.
7. Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 1993;53:3579-84. (Pubitemid 23229640)
8. Bjornsti MA, Houghton PJ. The tor pathway: a target for cancer therapy. Nat Rev Cancer 2004;4:335-48. (Pubitemid 38579480)
9. Bader AG, Kang S, Zhao L, Vogt PK. Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer 2005;5:921-9. (Pubitemid 41766781)
10. Amornphimoltham P, Sriuranpong V, Patel V, Benavides F, Conti CJ, Sauk J, et al. Persistent activation of the Akt pathway in head and neck squamous cell carcinoma: a potential target for UCN-01. Clin Cancer Res 2004;10:4029-37. (Pubitemid 38812478)
11. Wu HT, Ko SY, Fong JH, Chang KW, Liu TY, Kao SY. Expression of phosphorylated Akt in oral carcinogenesis and its induction by nicotine and alkaline stimulation. J Oral Pathol Med 2009;38:206-13.
12. Nathan CO, Amirghahari N, Rong X, Giordano T, Sibley D, Nordberg M, et al. Mammalian target of rapamycin inhibitors as possible adjuvant therapy for microscopic residual disease in head and neck squamous cell cancer. Cancer Res 2007;67:2160-8. (Pubitemid 46424235)
13. Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS, Workman P. Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises. Curr Opin Pharmacol 2008;8:393-412.
14. Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008;27:5497-510.
15. 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)
16. Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol 2010;28:1075-83.
17. Glaser R, Zhang HY, Yao KT, Zhu HC, Wang FX, Li GY, et al. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas. Proc Natl Acad Sci U S A 1989;86:9524-8. (Pubitemid 20010459)
18. Iwai-Kanai E, Yuan H, Huang C, Sayen MR, Perry-Garza CN, Kim L, et al. A method to measure cardiac autophagic flux in vivo. Autophagy 2008;4:322-9. (Pubitemid 351458093)
19. Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, et al. A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res 2001;61:439-44. (Pubitemid 32128593)
20. Cho DC, Cohen MB, Panka DJ, Collins M, Ghebremichael M, Atkins MB, et al. The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma. Clin Cancer Res 2010;16:3628-38.
21. Sourbier C, Lindner V, Lang H, Agouni A, Schordan E, Danilin S, et al. The phosphoinositide 3-kinase/Akt pathway: a new target in human renal cell carcinoma therapy. Cancer Res 2006;66:5130-42. (Pubitemid 43844935)
22. Or YY, Hui AB, To KF, Lam NY, Lo KW. PIK3CA mutations in nasopharyngeal carcinoma. Int J Cancer 2006;118:1065-7.
23. Qiu W, Schönleben F, Li X, Ho DJ, Close LG, Manolidis S, et al. PIK3CA mutations in head and neck squamous cell carcinoma. Clin Cancer Res 2006;12:1441-6.
24. Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 2008;4: 151-75.
25. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000;19: 5720-8.
26. Seglen PO, Gordon PB. 3-Methyladenine: specific inhibitor of autophagic/ lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci U S A 1982;79:1889-92. (Pubitemid 12088533)
27. Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 2007;25:2171-7. (Pubitemid 46954639)
28. Pedrero JM, Carracedo DG, PintoCM, Zapatero AH, Rodrigo JP, Nieto CS, et al. Frequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma. Int J Cancer 2005;114:242-8. (Pubitemid 40194293)
29. Lim KH, Counter CM. Reduction in the requirement of oncogenic Ras signaling to activation of PI3K/AKT pathway during tumor maintenance. Cancer Cell 2005;8:381-92. (Pubitemid 41579833)
30. Perrone F, Lampis A, Orsenigo M, Di Bartolomeo M, Gevorgyan A, Losa M, et al. PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients. Ann Oncol 2009;20:84-90.
31. Bouali S, Chrétien AS, Ramacci C, Rouyer M, Marchal S, Galenne T, et al. P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab. Cancer Gene Ther 2009;16:498-507.
32. Kozaki KI, Imoto I, Pimkhaokham A, Hasegawa S, Tsuda H, Omura K, et al. PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma. Cancer Sci 2006;97:1351-8. (Pubitemid 44614987)
33. Wang J, Kuropatwinski K, Hauser J, Rossi MR, Zhou Y, Conway A, et al. Colon carcinoma cells harboring PIK3CA mutations display resistance to growth factor deprivation induced apoptosis. Mol Cancer Ther 2007;6:1143-50. (Pubitemid 46554585)
34. 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.
35. Fatrai S, Elghazi L, Balcazar N, Cras-Méneur C, Krits I, Kiyokawa H, et al. Akt induces β-cell proliferation by regulating cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4 activity. Diabetes 2006;55:318-25. (Pubitemid 43343259)
36. Mukherji A, Janbandhu VC, Kumar V. GSK-3beta-dependent destabilization of cyclin D1 mediates replicational stress-induced arrest of cell cycle. FEBS Lett 2008;582:1111-6.
37. Rousseau D, Kaspar R, Rosenwald I, Gehrke L, Sonenberg N. Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E. Proc Natl Acad Sci U S A 1996;93: 1065-70. (Pubitemid 26054368)
38. Zou CY, Smith KD, Zhu QS, Liu J, McCutcheon IE, Slopis JM, et al. Dual targeting of AKT and mammalian target of rapamycin: a potential therapeutic approach for malignant peripheral nerve sheath tumor. Mol Cancer Ther 2009;8:1157-68.
39. Zhou BP, Liao Y, Xia W, Spohn B, Lee MH, Hung MC. Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat Cell Biol 2001;3:245-52. (Pubitemid 32201319)
40. Gottschalk AR, Doan A, Nakamura JL, Haas-Kogan DA, Stokoe D. Inhibition of phosphatidylinositol-3-kinase causes cell death through a protein kinase B (PKB)-dependent mechanism and growth arrest through a PKB-independent mechanism. Int J Radiat Oncol Biol Phys 2005;61:1183-8. (Pubitemid 40340914)
41. Reed JC. Drug Insight: cancer therapy strategies based on restoration of endogenous cell death mechanisms. Nat Clin Prac Oncol 2006;3: 388-98. (Pubitemid 44027293)
42. White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer. Clin Cancer Res 2009;15:5308-16.
43. Bröker LE, Kruyt FA, Giaccone G. Cell death independent of caspases: a review. Clin Cancer Res 2005;11:3155-62. (Pubitemid 40627860)
44. Ha SD, Ham B, Mogridge J, Saftig P, Lin S, Kim SO. Cathepsin Bmediated autophagy flux facilitates the anthrax toxin receptor 2- mediated delivery of anthrax lethal factor into the cytoplasm. J Biol Chem 2010;285:2120-9.
45. Aymard E, Barruche V, Naves T, Bordes S, Closs B, Verdier M, Ratinaud MH. Autophagy in human keratinocytes: an early step of the differentiation? Exp Dermatol 2011;20:263-8.
46. Aziz SA, Jilaveanu LB, Zito C, Camp RL, Rimm DL, Conrad P, et al. Vertical targeting of the phosphatidylinositol-3 kinase pathway as a strategy for treating melanoma. Clin Cancer Res 2010;16: 6029-39.