哺乳动物雷帕霉素靶蛋白信号通路与淋巴瘤的治疗研究进展_West China Medical Journal

Authors：

 马涛 ,  李晓明 , 邢宏运

泸州医学院附属医院血液内科（四川泸州 646000）;

Corresponding author：

马涛, Email: amatao@126.com; 李晓明, Email: lxm6358@21cn.com

Keywords：

哺乳动物雷帕霉素靶蛋白信号通路; 淋巴瘤; 治疗

DOI：

10.7507/1002-0179.20150512

Video：

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Abstract Full text Figures/Tables Video References Cited by

哺乳动物雷帕霉素靶蛋白（mTOR）广泛存在于细胞中，可感受来自于细胞内外的信号，调节细胞增殖、生长、细胞凋亡、血管生成及调控细胞周期。mTOR信号传导通路的活化与多种肿瘤相关，多项对血液系统恶性疾病的研究表明，其与白血病、淋巴瘤的发病密切相关。现对mTOR信号通路的组成及其作用机制进行阐述，并着重对mTOR信号通路抑制剂与多种淋巴瘤的治疗研究进行综述。

Citation： 马涛, 李晓明, 邢宏运. 哺乳动物雷帕霉素靶蛋白信号通路与淋巴瘤的治疗研究进展. West China Medical Journal, 2015, 30(9): 1789-1792. doi: 10.7507/1002-0179.20150512 Copy

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2.	Xu ZZ, Xia ZG, Wang AH, et al. Activation of the PI3K/AKT/mTOR pathway in diffuse large B cell lymphoma:clinical significance and inhibitory effect of rituximab[J]. Ann Hematol, 2013, 92(10):1351-1358.
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15.	Waldron JS, Yang I, Han S, et al. Implications for immunotherapy of tumor-mediated T-cell apoptosis associated with loss of the tumor suppressor PTEN in glioblastoma[J]. J Clin Neurosci, 2010, 17(12):1543-1547.
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17.	Castaneda CA, Cortes-Funes H, Gomez HL, et al. The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer[J]. Cancer Metastasis Rev, 2010, 29(4):751-759.
18.	Xu ZZ, Wang WF, Fu WB, et al. Combination of rituximab and mammalian target of rapamycin inhibitor everolimus (RAD001) in diffuse large B-cell lymphoma[J]. Leuk Lymphoma, 2014, 55(5):1151-1157.
19.	Wanner K, Hipp S, Oelsner M, et al. Mammalian target of rapamycin inhibition induces cell cycle arrest in diffuse large B cell lymphoma (DLBCL) cells and sensitises DLBCL cells to rituximab[J]. Br J Haematol, 2006, 134(5):475-484.
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24.	Ghobrial IM, Gertz M, Laplant B, et al. Phase Ⅱ trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia[J]. J Clin Oncol, 2010, 28(8):1408-1414.
25.	Roccaro AM, Sacco A, Husu EN, et al. Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy in Waldenstrom macroglobulinemia[J]. Blood, 2010, 115(3):559-569.
26.	Moskowitz AJ. Novel agents in hodgkin lymphoma[J]. Curr Oncol Rep, 2012, 14(5):419-423.
27.	Johnston PB, Inwards DJ, Colgan JP, et al. A phase Ⅱ trial of the oral mTOR inhibitor everoliums in relapsed Hodgkin lymphoma[J]. Am J Hematol, 2010, 85(5):320-324.

1. Schalm SS, Fingar DC, Sabatini DM, et al. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function[J]. Curr Biol, 2003, 13(10):797-806.
2. Xu ZZ, Xia ZG, Wang AH, et al. Activation of the PI3K/AKT/mTOR pathway in diffuse large B cell lymphoma:clinical significance and inhibitory effect of rituximab[J]. Ann Hematol, 2013, 92(10):1351-1358.
3. Müller A, Zang C, Chumduri C, et al. Concurrent inhibition of PI3K and mTORC1/mTORC2 overcomes resistance to rapamycin induced apoptosis by down-regulation of Mcl-1 in mantle cell lymphoma[J]. Int J Cancer, 2013, 133(8):1813-1824.
4. Vega F, Medeiros LJ, Leventaki V, et al. Activation of mammalian target of rapamycin signaling pathway contributes to tumor cell survival in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma[J]. Cancer Res, 2006, 66(13):6589-6597.
5. Márk Á, Hajdu M, Váradi Z, et al. Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease-a combined tissue microarray, in vitro and in vitro study[J]. BMC Cancer, 2013, 13:250.
6. Hay N, Sonenberg N. Upstream and downstream of mTOR[J]. Genes Dev, 2004, 18(16):1926-1945.
7. Zoncu R, Efeyan A, Sabatini DM. mTOR:from growth signal integration to cancer, diabetes and ageing[J]. Nat Rev Mol Cell Biol, 2011, 12(1):21-35.
8. Hara K, Maruki Y, Long X, et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action[J]. Cell, 2002, 110(2):177-189.
9. Huang SL, Houghton PJ. Targeting mTOR signaling for cancer therapy[J]. Curr Opin Pharmacol, 2003, 3(4):371-377.
10. Groenewoud MJ, Goorden SM, Kassies J, et al. Mammalian target of rapamycin complex Ⅰ (mTORC1) activity in ras homologue enriched in brain (Rheb)-deficient mouse embryonic fibroblasts[J]. PLoS One, 2013, 8(11):e81649.
11. Rhoads RE. eIF4E:new family members, new binding partners, new roles[J]. J Biol Chem, 2009, 284(25):16711-16715.
12. Ayuso MI, Hernández-Jiménez M, Martín ME, et al. New hierarchical phosphorylation pathway of the translational repressor eIF4E-binding protein 1 (4E-BP1) in ischemia-reperfusion stress[J]. J Biol Chem, 2010, 285(45):34355-34363.
13. Livingstone M, Bidinosti M. Rapamycin-insensitive mTORC1 activity controls eIF4E:4E-BP1 binding[J]. F1000 Res, 2012, 1:4.
14. Hara K, Yonezawa K, Weng QP, et al. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism[J]. J Biol Chem, 1998, 273(23):14484-14494.
15. Waldron JS, Yang I, Han S, et al. Implications for immunotherapy of tumor-mediated T-cell apoptosis associated with loss of the tumor suppressor PTEN in glioblastoma[J]. J Clin Neurosci, 2010, 17(12):1543-1547.
16. Ching CB, Hansel DE. Expanding therapeutic targets in bladder cancer:the PI3K/Akt/mTOR pathway[J]. Lab Invest, 2010, 90(10):1406-1414.
17. Castaneda CA, Cortes-Funes H, Gomez HL, et al. The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer[J]. Cancer Metastasis Rev, 2010, 29(4):751-759.
18. Xu ZZ, Wang WF, Fu WB, et al. Combination of rituximab and mammalian target of rapamycin inhibitor everolimus (RAD001) in diffuse large B-cell lymphoma[J]. Leuk Lymphoma, 2014, 55(5):1151-1157.
19. Wanner K, Hipp S, Oelsner M, et al. Mammalian target of rapamycin inhibition induces cell cycle arrest in diffuse large B cell lymphoma (DLBCL) cells and sensitises DLBCL cells to rituximab[J]. Br J Haematol, 2006, 134(5):475-484.
20. Witzig TE, Geyer SM, Ghobrial I, et al. Phase Ⅱ trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma[J]. J Clin Oncol, 2005, 23(23):5347-5356.
21. Coiffier B. Clinical efficacy and management of temsirolimus in patients with relapsed or refractory mantle cell lymphoma[J]. Clin Lymphoma Myeloma Leuk, 2013, 13(4):351-359.
22. Smith SM, van Besien K, Karrison T, et al. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes:the University of Chicago phase Ⅱ consortium[J]. J Clin Oncol, 2010, 28(31):4740-4746.
23. Saint-Hubert MD, Brepoels L, Devos E, et al. Molecular imaging of therapy response with (18)F-FLT and (18)F-FDG following cyclophosphamide and mTOR inhibition[J]. Am J Nucl Med Mol Imaging, 2012, 2(1):110-121.
24. Ghobrial IM, Gertz M, Laplant B, et al. Phase Ⅱ trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia[J]. J Clin Oncol, 2010, 28(8):1408-1414.
25. Roccaro AM, Sacco A, Husu EN, et al. Dual targeting of the PI3K/Akt/mTOR pathway as an antitumor strategy in Waldenstrom macroglobulinemia[J]. Blood, 2010, 115(3):559-569.
26. Moskowitz AJ. Novel agents in hodgkin lymphoma[J]. Curr Oncol Rep, 2012, 14(5):419-423.
27. Johnston PB, Inwards DJ, Colgan JP, et al. A phase Ⅱ trial of the oral mTOR inhibitor everoliums in relapsed Hodgkin lymphoma[J]. Am J Hematol, 2010, 85(5):320-324.

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哺乳动物雷帕霉素靶蛋白信号通路与淋巴瘤的治疗研究进展

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