Evidence of mTOR activation by an AKT-independent mechanism provides support for the combined treatment of PTEN-deficient prostate tumors with mTOR and AKT inhibitors

Translational Oncology

Volumn 5, Issue 6, 2012, Pages 422-429

  Zhang, Weisheng ^a   Haines, Brian B ^a   Efferson, Clay ^a   Zhu, Joe ^a   Ware, Chris ^a   Kunii, Kaiko ^a   Tammam, Jennifer ^a   Angagaw, Minilik ^a   Hinton, Marlene C ^a   Keilhack, Heike ^a   Paweletz, Cloud P ^a   Zhang, Theresa ^a   Winter, Chris ^a   Sathyanarayanan, Sriram ^a   Cheng, Jonathan ^a   Zawel, Leigh ^a   Fawell, Stephen ^a   Gilliland, Gary ^a   Majumder, Pradip K ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

8 [4 (1 AMINOCYCLOBUTYL) PHENYL] 9 PHENYL 1, 2, 4 TRIAZOLO [3, 4 F] [1, 6] NAPHTHYRIDIN 3 (2H) ONE; MAMMALIAN TARGET OF RAPAMYCIN; MESSENGER RNA; PHOSPHATIDYLINOSITOL 3, 4, 5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RIDAFOROLIMUS; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CLINICAL ASSESSMENT; CONTROLLED STUDY; ENZYME ACTIVATION; HISTOLOGY; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PROSTATE TUMOR; PROTEIN MICROARRAY; THREE DIMENSIONAL IMAGING; TUMOR VOLUME; WESTERN BLOTTING;

EID: 84871683750     PISSN: None     EISSN: 19365233     Source Type: Journal    
DOI: 10.1593/tlo.12241     Document Type: Article

References (44)

1. Baade PD, Coory MD, and Aitken JF (2004). International trends in prostatecancer mortality: the decrease is continuing and spreading. Cancer Causes Control 15, 237-241.
2. Yap TA, Zivi A, Omlin A, and de Bono JS (2011). The changing therapeutic landscape of castration-resistant prostate cancer. Nat Rev Clin Oncol 8, 597-610.
3. Michaelson MD, Cotter SE, Gargollo PC, Zietman AL, Dahl DM, and Smith MR (2008). Management of complications of prostate cancer treatment. CA Cancer J Clin 58, 196-213.
4. Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Gil T, et al. (1997). Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 337, 295-300.
5. Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS, and Yao SL (2008). Survival following primary androgen deprivation therapy among men with localized prostate cancer. JAMA 300, 173-181.
6. Pomerantz M and Kantoff P (2007). Advances in the treatment of prostate cancer. Annu Rev Med 58, 205-220.
7. Xu Y, Chen SY, Ross KN, and Balk SP (2006). Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and posttranscriptional increases in cyclin D proteins. Cancer Res 66, 7783-7792.
8. Sun M, Yang L, Feldman RI, Sun XM, Bhalla KN, Jove R, Nicosia SV, and Cheng JQ (2003). Activation of phosphatidylinositol 3-kinase/AKT pathway by androgen through interaction of p85α, androgen receptor, and Src. J Biol Chem 278, 42992-43000.
9. Baron S, Manin M, Beaudoin C, Leotoing L, Communal Y, Veyssiere G, and Morel L (2004). Androgen receptor mediates non-genomic activation of phosphatidylinositol 3-OH kinase in androgen-sensitive epithelial cells. J Biol Chem 279, 14579-14586.
10. Zhang W, Zhu J, Efferson CL, Ware C, Tammam J, Angagaw M, Laskey J, Bettano KA, Kasibhatla S, Reilly JF, et al. (2009). Inhibition of tumor growth progression by antiandrogens and mTOR inhibitor in a Pten-deficient mouse model of prostate cancer. Cancer Res 69, 7466-7472.
11. Myers MP, Stolarov JP, Eng C, Li J, Wang SI, Wigler MH, Parsons R, and Tonks NK (1997). P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc Natl Acad Sci USA 94, 9052-9057.
12. Aoki M, Batista O, Bellacosa A, Tsichlis P, and Vogt PK (1998). The Akt kinase: molecular determinants of oncogenicity. Proc Natl Acad Sci USA 95, 14950-14955.
13. Neshat MS, Mellinghoff IK, Tran C, Stiles B, Thomas G, Petersen R, Frost P, Gibbons JJ, Wu H, and Sawyers CL (2001). Enhanced sensitivity of PTENdeficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci USA 98, 10314-10319.
14. Podsypanina K, Lee RT, Politis C, Hennessy I, Crane A, Puc J, Neshat M, Wang H, Yang L, Gibbons J, et al. (2001). An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/-mice. Proc Natl Acad Sci USA 98, 10320-10325.
15. Stiles B, Gilman V, Khanzenzon N, Lesche R, Li A, Qiao R, Liu X, and Wu H (2002). Essential role of AKT-1/protein kinase Bα in PTEN-controlled tumorigenesis. Mol Cell Biol 22, 3842-3851.
16. Gray IC, Phillips SM, Lee SJ, Neoptolemos JP, Weissenbach J, and Spurr NK (1995). Loss of the chromosomal region 10q23-25 in prostate cancer. Cancer Res 55, 4800-4803.
17. Komiya A, Suzuki H, Ueda T, Yatani R, Emi M, Ito H, and Shimazaki J (1996). Allelic losses at loci on chromosome 10 are associated with metastasis and progression of human prostate cancer. Genes Chromosomes Cancer 17, 245-253.
18. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, et al. (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275, 1943-1947.
19. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, et al. (1997). Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15, 356-362.
20. Suzuki H, Freije D, Nusskern DR, Okami K, Cairns P, Sidransky D, Isaacs WB, and Bova GS (1998). Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues. Cancer Res 58, 204-209.
21. Di Cristofano A, Pesce B, Cordon-Cardo C, and Pandolfi PP (1998). Pten is essential for embryonic development and tumour suppression. Nat Genet 19, 348-355.
22. Podsypanina K, Ellenson LH, Nemes A, Gu J, Tamura M, Yamada KM, Cordon-Cardo C, Catoretti G, Fisher PE, and Parsons R (1999). Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc Natl Acad Sci USA 96, 1563-1568.
23. Majumder PK and Sellers WR (2005). Akt-regulated pathways in prostate cancer. Oncogene 24, 7465-7474.
24. Engelman JA, Luo J, and Cantley LC (2006). The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 7, 606-619.
25. Vivanco I and Sawyers CL (2002). The phosphatidylinositol 3-kinase-AKT pathway in human cancer. Nat Rev Cancer 2, 489-501.
26. Majumder PK, Yeh JJ, George DJ, Febbo PG, Kum J, Xue Q, Bikoff R, Ma H, Kantoff PW, Golub TR, et al. (2003). Prostate intraepithelial neoplasia induced by prostate restricted AKT activation: the MPAKT model. Proc Natl Acad Sci USA 100, 7841-7846.
27. Majumder PK, Grisanzio C, O'Connell F, Barry M, Brito JM, Xu Q, Guney I, Berger R, Herman P, Bikoff R, et al. (2008). A prostatic intraepithelial neoplasiadependent p27Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression. Cancer Cell 14, 146-155.
28. Wang S, Gao J, Lei Q, Rozengurt N, Pritchard C, Jiao J, Thomas GV, Li G, Roy-Burman P, Nelson PS, et al. (2003). Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4, 209-221.
29. Lesche R, Groszer M, Gao J, Wang Y, Messing A, Sun H, Liu X, and Wu H (2002). Cre/loxP-mediated inactivation of the murine Pten tumor suppressor gene. Genesis 32, 148-149.
30. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, et al. (2006). mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66, 1500-1508.
31. Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H, and Khuri FR (2005). Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 65, 7052-7058.
32. Sarbassov DD, Guertin DA, Ali SM, and Sabatini DM (2005). Phosphorylation and regulation of Akt/PKBby the rictor-mTOR complex. Science 307, 1098-1101.
33. Wu X, Wu J, Huang J, Powell WC, Zhang J, Matusik RJ, Sangiorgi FO, Maxson RE, Sucov HM, and Roy-Burman P (2001). Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech Dev 101, 61-69.
34. Hirai H, Sootome H, Nakatsuru Y, Miyama K, Taguchi S, Tsujioka K, Ueno Y, Hatch H, Majumder PK, Pan BS, et al. (2010). MK-2206, an allosteric Akt inhibitor, enhances anti-tumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther 9(7), 1956-1967.
35. Rivera VM, Squillace RM, Miller D, Berk L, Wardwell SD, Ning Y, Pollock R, Narasimhan NI, Iuliucci JD, Wang F, et al. (2011). Ridaforolimus (AP23573; MK-8669), a potent mTOR inhibitor, has broad antitumor activity and can be optimally administered using intermittent dosing regimens. Mol Cancer Ther 10, 1059-1071.
36. Efferson CL, Winkelmann CT, Ware C, Sullivan T, Giampaoli S, Tammam J, Patel S, Mesiti G, Reilly JF, Gibson RE, et al. (2010). Downregulation of Notch pathway by a γ-secretase inhibitor attenuates AKT/mTOR signaling and glucose uptake in an ERBB-2 transgenic breast cancer model. Cancer Res 70, 2476-2484.
37. Tammam J, Ware C, Efferson C, O'Neil J, Rao S, Qu X, Gorenstein J, Angagaw M, Kim H, Kenific C, et al. (2009). Down-regulation of the Notch pathway mediated by a γ-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia. Br J Pharmacol 158, 1183-1195.
38. Pienta KJ and Smith DC (2005). Advances in prostate cancer chemotherapy: a new era begins. CA Cancer J Clin 55, 300-318. quiz 23-5.
39. Carver BS, Chapinski C, Wongvipat J, Hieronymus H, Chen Y, Chandarlapaty S, Arora VK, Le C, Koutcher J, Scher H, et al. (2011). Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 19, 575-586.
40. Kinkade CW, Castillo-Martin M, Puzio-Kuter A, Yan J, Foster TH, Gao H, Sun Y, Ouyang X, Gerald WL, Cordon-Cardo C, et al. (2008). Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model. J Clin Invest 118, 3051-3064.
41. Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, Egia A, Sasaki AT, Thomas G, Kozma SC, et al. (2008). Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest 118, 3065-3074.
42. Cloughesy TF, Yoshimoto K, Nghiemphu P, Brown K, Dang J, Zhu S, Hsueh T, Chen Y, Wang W, Youngkin D, et al. (2008). Antitumor activity of rapamycin in a phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med 5, e8.
43. Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR, et al. (2004). mTOR inhibition reverses AKT-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 10(6), 594-601.
44. Squillace RM, Miller D, Wardwell SD, Wang F, Clackson T, and Rivera VM (2012). Synergistic activity of the mTOR inhibitor ridaforolimus and the antiandrogen bicalutamide in prostate cancer models. Int J Oncol 41, 425-432.