Combined inhibition of PI3K-related DNA damage response kinases and mTORC1 induces apoptosis in MYC-driven B-cell lymphomas

Blood

Volumn 121, Issue 15, 2013, Pages 2964-2974

  Shortt, Jake ^a,b   Martin, Benjamin P ^a,b   Newbold, Andrea ^a,b   Hannan, Katherine M ^a,b   Devlin, Jennifer R ^a,b   Baker, Adele J ^a,b   Ralli, Rachael ^a,b   Cullinane, Carleen ^a,b   Schmitt, Clemens A ^c,d   Reimann, Maurice ^c   Hall, Michael N ^e   Wall, Meaghan ^a,b   Hannan, Ross D ^a,b   Pearson, Richard B ^a,b   McArthur, Grant A ^a,b   Johnstone, Ricky W ^a,b  

^a PETER MACCALLUM CANCER CENTRE   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^d MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^e UNIVERSITY OF BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

2 MORPHOLINO 6 (1 THIANTHRENYL) 4 PYRANONE; BH3 PROTEIN; BUPARLISIB; CRE RECOMBINASE; DACTOLISIB; EVEROLIMUS; HISTONE H2AX; KU 57788; KU 63794; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN P53; RAPAMYCIN; UNCLASSIFIED DRUG; DDR1 PROTEIN, HUMAN; H2AX PROTEIN, MOUSE; HISTONE; IMIDAZOLE DERIVATIVE; MULTIPROTEIN COMPLEX; MYC PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; QUINOLINE DERIVATIVE; TARGET OF RAPAMYCIN KINASE; TOR COMPLEX 1;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; B CELL LYMPHOMA; BURKITT LYMPHOMA; CELL VIABILITY; CONTROLLED STUDY; DNA DAMAGE; DRUG EFFECT; GENE OVEREXPRESSION; IC 50; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; ONCOGENE MYC; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DEPHOSPHORYLATION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; TUMOR LOCALIZATION; UPREGULATION; ANIMAL; C57BL MOUSE; CELL LINE; DOSE RESPONSE; DRUG ANTAGONISM; FLOW CYTOMETRY; GENETICS; HUMAN; METABOLISM; MOUSE MUTANT; PATHOLOGY; PHOSPHORYLATION; SURVIVAL; TUMOR CELL CULTURE; WESTERN BLOTTING;

ANIMALS; APOPTOSIS; BLOTTING, WESTERN; CELL LINE; DNA DAMAGE; DOSE-RESPONSE RELATIONSHIP, DRUG; FLOW CYTOMETRY; HISTONES; HUMANS; IMIDAZOLES; LYMPHOMA, B-CELL; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MULTIPROTEIN COMPLEXES; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-MYC; QUINOLINES; RECEPTOR PROTEIN-TYROSINE KINASES; SURVIVAL ANALYSIS; TOR SERINE-THREONINE KINASES; TUMOR CELLS, CULTURED;

MLCS; MLOWN;

EID: 84879437606     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2012-08-446096     Document Type: Article

References (50)

1. Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer. 2008;8(12):976-990.
2. Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3452-3459.
3. Green TM, Young KH, Visco C, et al. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3460-3467.
4. Klapproth K, Wirth T. Advances in the understanding of MYC-induced lymphomagenesis. Br J Haematol. 2010;149(4):484-497.
5. Vita M, Henriksson M. The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol. 2006;16(4):318-330. (Pubitemid 44311040)
6. Mead GM, Sydes MR, Walewski J, et al; UKLG LY06 collaborators. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol. 2002;13(8):1264-1274. (Pubitemid 34960136)
7. Fan S, el-Deiry WS, Bae I, et al. p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. Cancer Res. 1994;54(22):5824-5830.
8. Hess G, Herbrecht R, Romaguera J, et al. Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009;27(23):3822- 3829.
9. Witzig TE, Gupta M. Signal transduction inhibitor therapy for lymphoma. Hematology Am Soc Hematol Educ Program. 2010;2010:265-270.
10. Han SS, Yun H, Son DJ, et al. NF-kappaB/STAT3/PI3K signaling crosstalk in iMyc E mu B lymphoma. Mol Cancer. 2010;9:97.
11. Wendel HG, De Stanchina E, Fridman JS, et al. Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature. 2004;428(6980):332-337. (Pubitemid 38418805)
12. Ruggero D, Montanaro L, Ma L, et al. The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat Med. 2004;10(5):484-486. (Pubitemid 38667906)
13. Al-Ejeh F, Kumar R, Wiegmans A, et al. Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes. Oncogene. 2010;29(46):6085-6098.
14. Vafa O, Wade M, Kern S, et al. c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability. Mol Cell. 2002;9(5):1031-1044. (Pubitemid 34626672)
15. Reimann M, Loddenkemper C, Rudolph C, et al. The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo. Blood. 2007;110(8):2996-3004. (Pubitemid 350006954)
16. Mills JR, Hippo Y, Robert F, et al. mTORC1 promotes survival through translational control of Mcl-1. Proc Natl Acad Sci USA. 2008;105(31):10853- 10858.
17. Ravitz MJ, Chen L, Lynch M, et al. c-myc Repression of TSC2 contributes to control of translation initiation and Myc-induced transformation. Cancer Res. 2007;67(23):11209-11217. (Pubitemid 350248546)
18. Wendel HG, Malina A, Zhao Z, et al. Determinants of sensitivity and resistance to rapamycin-chemotherapy drug combinations in vivo. Cancer Res. 2006;66(15):7639-7646. (Pubitemid 44289221)
19. Sarbassov DD, Guertin DA, Ali SM, et al. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307(5712):1098-1101. (Pubitemid 40262113)
20. Carracedo A, Ma L, Teruya-Feldstein J, et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest. 2008;118(9):3065-3074.
21. O'Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006;66(3):1500-1508. (Pubitemid 43259931)
22. Sun SY, Rosenberg LM, Wang X, et al. Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res. 2005;65(16):7052-7058. (Pubitemid 41161231)
23. Maira SM, Stauffer F, Brueggen J, et al. Identification and characterization of NVPBEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 2008;7(7):1851-1863.
24. Bhatt AP, Bhende PM, Sin SH, et al. Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas. Blood. 2010;115(22):4455-4463.
25. Chiarini F, Grimaldi C, Ricci F, et al. Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVPBEZ235 against T-cell acute lymphoblastic leukemia. Cancer Res. 2010;70(20):8097-8107.
26. McMillin DW, Ooi M, Delmore J, et al. Antimyeloma activity of the orally bioavailable dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235. Cancer Res. 2009;69(14):5835-5842.
27. Adams JM, Harris AW, Pinkert CA, et al. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985;318(6046):533-538. (Pubitemid 16173038)
28. Yang DQ, Kastan MB. Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1. Nat Cell Biol. 2000;2(12):893-898.
29. Grespi F, Soratroi C, Krumschnabel G, et al. BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis. Cell Death Differ. 2010;17(11):1672-1683.
30. Patursky-Polischuk I, Stolovich-Rain M, Hausner-Hanochi M, et al. The TSC-mTOR pathway mediates translational activation of TOP mRNAs by insulin largely in a raptor- or rictor-independent manner. Mol Cell Biol. 2009;29(3):640-649.
31. Villunger A, Michalak EM, Coultas L, et al. p53-and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science. 2003;302(5647):1036-1038. (Pubitemid 37386194)
32. Egle A, Harris AW, Bouillet P, et al. Bim is a suppressor of Myc-induced mouse B cell leukemia. Proc Natl Acad Sci USA. 2004;101(16):6164-6169. (Pubitemid 38520545)
33. Wiegmans AP, Alsop AE, Bots M, et al. Deciphering the molecular events necessary for synergistic tumor cell apoptosis mediated by the histone deacetylase inhibitor vorinostat and the BH3 mimetic ABT-737. Cancer Res. 2011;71(10):3603-3615.
34. Lindemann RK, Newbold A, Whitecross KF, et al. Analysis of the apoptotic and therapeutic activities of histone deacetylase inhibitors by using a mouse model of B cell lymphoma. Proc Natl Acad Sci USA. 2007;104(19):8071-8076. (Pubitemid 47185877)
35. Spike BT, Dirlam A, Dibling BC, et al. The Rb tumor suppressor is required for stress erythropoiesis. EMBO J. 2004;23(21):4319-4329. (Pubitemid 39546169)
36. Cullinane C, Dorow DS, Kansara M, et al. An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development. Cancer Res. 2005;65(21):9633-9636. (Pubitemid 41541437)
37. Beebe SJ, Holloway R, Rannels SR, et al. Two classes of cAMP analogs which are selective for the two different cAMP-binding sites of type II protein kinase demonstrate synergism when added together to intact adipocytes. J Biol Chem. 1984;259(6):3539-3547. (Pubitemid 14170082)
38. Kong D, Yaguchi S, Yamori T. Effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, on DNA-dependent protein kinase. Biol Pharm Bull. 2009;32(2):297-300.
39. Azad A, Jackson S, Cullinane C, et al. Inhibition of DNA-dependent protein kinase induces accelerated senescence in irradiated human cancer cells. Mol Cancer Res. 2011;9(12):1696-1707.
40. Mukherjee B, Tomimatsu N, Amancherla K, et al. The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKCs-mediated DNA damage responses. Neoplasia. 2012;14(1):34-43.
41. Eischen CM, Weber JD, Roussel MF, et al. Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev. 1999;13(20):2658-2669. (Pubitemid 29508553)
42. Wilda M, Bruch J, Harder L, et al. Inactivation of the ARF-MDM-2-p53 pathway in sporadic Burkitt's lymphoma in children. Leukemia. 2004;18(3):584-588. (Pubitemid 38425874)
43. Thoreen CC, Kang SA, Chang JW, et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem. 2009;284(12):8023-8032.
44. Peterson TR, Laplante M, Thoreen CC, et al. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009;137(5):873-886.
45. Li Y, Yang DQ. The ATM inhibitor KU-55933 suppresses cell proliferation and induces apoptosis by blocking Akt in cancer cells with overactivated Akt. Mol Cancer Ther. 2010;9(1):113-125.
46. Maira SM, Pecchi S, Huang A, et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther. 2012;11(2):317-328.
47. García-Martínez JM, Moran J, Clarke RG, et al. Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR). Biochem J. 2009;421(1):29-42.
48. Elliott SL, Crawford C, Mulligan E, et al. Mitoxantrone in combination with an inhibitor of DNA-dependent protein kinase: a potential therapy for high risk B-cell chronic lymphocytic leukaemia. Br J Haematol. 2011;152(1):61-71.
49. Datta SR, Dudek H, Tao X, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997;91(2):231-241. (Pubitemid 27456390)
50. Puthalakath H, Villunger A, O'Reilly LA, et al. Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science. 2001;293(5536):1829-1832. (Pubitemid 32845780)