Targeting PI3K/mTOR signaling displays potent antitumor efficacy against nonfunctioning pituitary adenomas

Clinical Cancer Research

Volumn 21, Issue 14, 2015, Pages 3204-3215

  Lee, Misu ^a   Wiedemann, Tobias ^a   Gross, Claudia ^b   Leinhäuser, Ines ^a   Roncaroli, Federico ^c   Braren, Rickmer ^b   Pellegata, Natalia S ^a  

^a INSTITUTE OF EPIDEMIOLOGY   (Germany)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BETA DEFENSIN 1; DACTOLISIB; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PLACEBO; ANTINEOPLASTIC AGENT; BETA DEFENSIN; DEFB1 PROTEIN, HUMAN; DEFB1 PROTEIN, RAT; DEFENSIN; IMIDAZOLE DERIVATIVE; QUINOLINE DERIVATIVE; TARGET OF RAPAMYCIN KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CELL PROLIFERATION; CELL SURVIVAL; CELL VIABILITY; CONTROLLED STUDY; CYTOTOXICITY; DEFB1 GENE; DIARRHEA; DIFFUSION WEIGHTED IMAGING; DRUG EFFICACY; DRUG POTENCY; DRUG TARGETING; ENZYME INHIBITION; GENE EXPRESSION PROFILING; HYPOPHYSIS CELL; IN VITRO STUDY; IN VIVO STUDY; NONFUNCTIONING PITUITARY ADENOMA; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; RAT; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; TUMOR CELL; TUMOR VOLUME; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; DISEASE MODEL; DRUG EFFECTS; FLUORESCENT ANTIBODY TECHNIQUE; GENE EXPRESSION REGULATION; HUMAN; HYPOPHYSIS TUMOR; MUTANT RAT STRAIN; PATHOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ANIMALS; ANTINEOPLASTIC AGENTS; BETA-DEFENSINS; DEFENSINS; DISEASE MODELS, ANIMAL; FLUORESCENT ANTIBODY TECHNIQUE; GENE EXPRESSION REGULATION; HUMANS; IMIDAZOLES; PHOSPHATIDYLINOSITOL 3-KINASES; PITUITARY NEOPLASMS; QUINOLINES; RATS; RATS, MUTANT STRAINS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

EID: 84942895438     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-0288     Document Type: Article

References (55)

1. Pereira AM, Biermasz NR. Treatment of nonfunctioning pituitary adenomas: what were the contributions of the last 10 years? A critical view. Ann Endocrinol 2012;73:111-6.
2. Greenman Y, Stern N. Non-functioning pituitary adenomas. Best Pract Res Clin Endocrinol Metab 2009;23:625-38.
3. Brochier S, Galland F, Kujas M, Parker F, Gaillard S, Raftopoulos C, et al. Factors predicting relapse of nonfunctioning pituitarymacroadenomas after neurosurgery: a study of 142 patients. Eur J Endocrinol 2010;163:193-200.
4. Losa M, Donofrio CA, Barzaghi R, Mortini P. Presentation and surgical results of incidentally discovered nonfunctioning pituitary adenomas: evidence for a better outcome independently of other patients' characteristics. Eur J Endocrinol 2013;169:735-42.
5. Berkmann S, Schlaffer S, Nimsky C, Fahlbusch R, Buchfelder M. Follow-up and long-term outcome of nonfunctioning pituitary adenoma operated by transsphenoidal surgery with intraoperative high-field magnetic resonance imaging. Acta Neurochir 2014;156:2233-43.
6. Colao A, Filippella M, Pivonello R, Di Somma C, Faggiano A, Lombardi G. Combined therapy of somatostatin analogues and dopamine agonists in the treatment of pituitary tumours. Eur J Endocrinol 2007;156 Suppl 1:S57-63.
7. Greenman Y, Tordjman K, Osher E, Veshchev I, Shenkerman G, Reider G I I, et al. Postoperative treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists decreases tumour remnant growth. Clin Endocrinol 2005;63:39-44.
8. Cantrell DA. Phosphoinositide 3-kinase signalling pathways. J Cell Sci 2001;114:1439-45.
9. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 2005;4:988-1004.
10. Lin Y, Jiang X, Shen Y, Li M, Ma H, Xing M, et al. Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors. Endocr Relat Cancer 2009;16:301-10.
11. Murat CB, Braga PB, Fortes MA, Bronstein MD, Correa-Giannella ML, Giorgi RR. Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas. Braz J Med Biol Res 2012;45:851-5.
12. Cakir M, Grossman AB. Targeting MAPK (Ras/ERK) and PI3K/Akt pathways in pituitary tumorigenesis. Expert Opin Ther Targets 2009;13:1121-34.
13. Monsalves E, Juraschka K, Tateno T, Agnihotri S, Asa SL, Ezzat S, et al. The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas. Endocr Relat Cancer 2014;21:R331-44.
14. Cerovac V, Monteserin-Garcia J, Rubinfeld H, Buchfelder M, Losa M, Florio T, et al. The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells. Cancer Res 2010;70:666-74.
15. Zatelli MC, Minoia M, Filieri C, Tagliati F, Buratto M, Ambrosio MR, et al. Effect of everolimus on cell viability in nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 2010;95:968-76.
16. Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, et al. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 2004;10:594-601.
17. Neshat MS, Mellinghoff IK, Tran C, Stiles B, Thomas G, Petersen R, et al. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci U S A 2001;98:10314-9.
18. Huang S, Houghton PJ. Resistance to rapamycin: a novel anticancer drug. Cancer Metastasis Rev 2001;20:69-78.
19. 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.
20. 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.
21. Baumann P, Mandl-Weber S, Oduncu F, Schmidmaier R. The novel orally bioavailable inhibitor of phosphoinositol-3-kinase andmammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma. Exp Cell Res 2009;315:485-97.
22. 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.
23. 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.
24. Cao P, Maira SM, Garcia-Echeverria C, Hedley DW. Activity of a novel, dual PI3-kinase/mTor inhibitor NVP-BEZ235 against primary human pancreatic cancers grown as orthotopic xenografts. Br J Cancer 2009;100:1267-76.
25. Pellegata NS. MENX and MEN4. Clinics 2012;67 Suppl 1:13-8.
26. Lee M, Theodoropoulou M, Graw J, Roncaroli F, Zatelli MC, Pellegata NS. Levels of p27 sensitize to dual PI3K/mTOR inhibition. Mol Cancer Ther 2011;10:1450-9.
27. Marinoni I, Lee M, Mountford S, Perren A, Bravi I, Jennen L, et al. Characterization of MENX-associated pituitary tumours. Neuropathol Appl Neurobiol 2013;39:256-69.
28. Lee M, Marinoni I, Irmler M, Psaras T, Honegger JB, Beschorner R, et al. Transcriptome analysis of MENX-associated rat pituitary adenomas identifies novel molecular mechanisms involved in the pathogenesis of human pituitary gonadotroph adenomas. Acta Neuropathol 2013;126:137-50.
29. Fritz A, Walch A, Piotrowska K, Rosemann M, Schaffer E, Weber K, et al. Recessive transmission of a multiple endocrine neoplasia syndrome in the rat. Cancer Res 2002;62:3048-51.
30. Lee M, Waser B, Reubi JC, Pellegata NS. Secretin receptor promotes the proliferation of endocrine tumor cells via the PI3K/AKT pathway. Mol Endocrinol 2012;26:1394-405.
31. Thoeny HC, Ross BD. Predicting and monitoring cancer treatment response with diffusion-weighted MRI. J Magn Reson Imaging 2010;32:2-16.
32. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB Jr, Ganz T. Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 1998;101:1633-42.
33. Mansour SC, Pena OM, Hancock RE. Host defense peptides: front-line immunomodulators. Trends Immunol 2014;35:443-50.
34. Han Q, Wang R, Sun C, Jin X, Liu D, Zhao X, et al. Human beta-defensin-1 suppresses tumor migration and invasion and is an independent predictor for survival of oral squamous cell carcinoma patients. PLoS ONE 2014;9:e91867.
35. Donald CD, Sun CQ, Lim SD, Macoska J, Cohen C, Amin MB, et al. Cancerspecific loss of beta-defensin 1 in renal and prostatic carcinomas. Lab Invest 2003;83:501-5.
36. Gambichler T, Skrygan M, Huyn J, Bechara FG, Sand M, Altmeyer P, et al. Pattern of mRNA expression of beta-defensins in basal cell carcinoma. BMC Cancer 2006;6:163.
37. Sun CQ, Arnold R, Fernandez-Golarz C, Parrish AB, Almekinder T, He J, et al. Human beta-defensin-1, a potential chromosome 8p tumor suppressor: control of transcription and induction of apoptosis in renal cell carcinoma. Cancer Res 2006;66:8542-9.
38. Windle JJ, Weiner RI, Mellon PL. Cell lines of the pituitary gonadotrope lineage derived by targeted oncogenesis in transgenicmice. Mol Endocrinol 1990;4:597-603.
39. Valentino JD, Li J, Zaytseva YY, Mustain WC, Elliott VA, Kim JT, et al. Cotargeting the PI3K and RAS pathways for the treatment of neuroendocrine tumors. Clin Cancer Res 2014;20:1212-22.
40. Dai C, Zhang B, Liu X, Ma S, Yang Y, Yao Y, et al. Inhibition of PI3K/AKT/mTOR pathway enhances temozolomide-induced cytotoxicity in pituitary adenoma cell lines in vitro and xenografted pituitary adenoma in female nude mice. Endocrinology 2013;154:1247-59.
41. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.
42. Iwasa H, Kubota K, Hamada N, Nogami M, Nishioka A. Early prediction of response to neoadjuvant chemotherapy in patients with breast cancer using diffusion-weighted imaging and gray-scale ultrasonography. Oncol Rep 2014;31:1555-60.
43. Schmidt S, Dunet V, Koehli M, Montemurro M, Meuli R, Prior JO. Diffusion-weighted magnetic resonance imaging in metastatic gastrointestinal stromal tumor (GIST): a pilot study on the assessment of treatment response in comparison with 18F-FDG PET/CT. Acta Radiol 2013;54:837-42.
44. Lim KS. Diffusion-weighted MRI of hepatocellular carcinoma in cirrhosis. Clin Radiol 2014;69:1-10.
45. Wang H, Fei B. Diffusion-weighted MRI formonitoring tumor response to photodynamic therapy. J Magn Reson Imaging 2010;32:409-17.
46. Jin JY, Zhou L, Wang Y, Li Z, Zhao JG, Zhang QY, et al. Antibacterial and antiviral roles of a fish beta-defensin expressed both in pituitary and testis. PLoS ONE 2010;5:e12883.
47. 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.
48. Sarker D, Reid AH, Yap TA, de Bono JS. Targeting the PI3K/AKT pathway for the treatment of prostate cancer. Clin Cancer Res 2009;15:4799-805.
49. Bose SK, Gibson W, Bullard RS, Donald CD. PAX2 oncogene negatively regulates the expression of the host defense peptide human beta defensin-1 in prostate cancer. Mol Immunol 2009;46:1140-8.
50. Shen W, Brown NS, Finn PF, Dice JF, Franch HA. Akt and Mammalian target of rapamycin regulate separate systems of proteolysis in renal tubular cells. J Am Soc Nephrol 2006;17:2414-23.
51. Ritz-Laser B, Estreicher A, Gauthier B, Philippe J. The paired homeodomain transcription factor Pax-2 is expressed in the endocrine pancreas and transactivates the glucagon gene promoter. J Biol Chem 2000;275:32708-15.
52. Hind CK, Carter MJ, Harris CL, Chan HT, James S, Cragg MS. The role of the pro-survival molecule Bfl-1 in melanoma. Int J Biochem Cell Biol 2015;59:94-102.
53. Brien G, Trescol-Biemont MC, Bonnefoy-Berard N. Downregulation of Bfl-1 protein expression sensitizes malignant B cells to apoptosis. Oncogene 2007;26:5828-32.
54. Brien G, Debaud AL, Bickle M, Trescol-Biemont MC, Moncorge O, Colas P, et al. Characterization of peptide aptamers targeting Bfl-1 anti-apoptotic protein. Biochemistry 2011;50:5120-9.
55. Jouanneau E, Wierinckx A, Ducray F, Favrel V, Borson-Chazot F, Honnorat J, et al. New targeted therapies in pituitary carcinoma resistant to temozolomide. Pituitary 2012;15:37-43.