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Promising activity of nelfinavir-bortezomib-dexamethasone in proteasome inhibitor-refractory multiple myeloma.奈非那韦-硼替佐米-地塞米松在蛋白酶体抑制剂难治性多发性骨髓瘤中显示出有前景的活性。
Blood. 2018 Nov 8;132(19):2097-2100. doi: 10.1182/blood-2018-05-851170. Epub 2018 Sep 20.
2
Treatment with the HIV protease inhibitor nelfinavir triggers the unfolded protein response and may overcome proteasome inhibitor resistance of multiple myeloma in combination with bortezomib: a phase I trial (SAKK 65/08).使用HIV蛋白酶抑制剂奈非那韦进行治疗可引发未折叠蛋白反应，并且与硼替佐米联合使用时可能克服多发性骨髓瘤对蛋白酶体抑制剂的耐药性：一项I期试验（SAKK 65/08）。
Haematologica. 2016 Mar;101(3):346-55. doi: 10.3324/haematol.2015.135780. Epub 2015 Dec 11.
3
Nelfinavir and lenalidomide/dexamethasone in patients with lenalidomide-refractory multiple myeloma. A phase I/II Trial (SAKK 39/10).来那度胺难治性多发性骨髓瘤患者中应用奈非那韦和来那度胺/地塞米松：一项 I/II 期试验（SAKK 39/10）。
Blood Cancer J. 2019 Aug 27;9(9):70. doi: 10.1038/s41408-019-0228-2.
4
Systems Modeling of Bortezomib and Dexamethasone Combinatorial Effects on Bone Homeostasis in Multiple Myeloma Patients.硼替佐米和地塞米松联合作用对多发性骨髓瘤患者骨稳态的系统建模。
J Pharm Sci. 2019 Jan;108(1):732-740. doi: 10.1016/j.xphs.2018.11.024. Epub 2018 Nov 22.
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Prominent regression of corneal crystalline deposits in multiple myeloma after treatment with proteasome inhibitor.蛋白酶体抑制剂治疗后多发性骨髓瘤患者角膜晶体沉积物显著消退
Ann Hematol. 2019 Mar;98(3):793-795. doi: 10.1007/s00277-019-03614-0. Epub 2019 Jan 15.
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Patient Characteristics and Outcomes of Relapsed/Refractory Multiple Myeloma in Patients Treated with Proteasome Inhibitors in Germany.在德国，接受蛋白酶体抑制剂治疗的复发性/难治性多发性骨髓瘤患者的特征和结局。
Oncol Res Treat. 2020;43(9):449-459. doi: 10.1159/000509018. Epub 2020 Jul 21.
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Bortezomib and Thalidomide Treatment Results in Newly Diagnosed Transplant-Ineligible Multiple Myeloma Patients are Comparable in Long-Term Follow-Up.硼替佐米与沙利度胺治疗新诊断的不适于移植的多发性骨髓瘤患者的长期随访结果具有可比性。
Klin Onkol. 2019 Fall;32(6):445-452. doi: 10.14735/amko2019445.
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Olaptesed pegol, an anti-CXCL12/SDF-1 Spiegelmer, alone and with bortezomib-dexamethasone in relapsed/refractory multiple myeloma: a Phase IIa Study.奥拉培塞德聚乙二醇，一种抗CXCL12/SDF-1 Spiegelmer，单药及与硼替佐米-地塞米松联合用于复发/难治性多发性骨髓瘤：一项IIa期研究。
Leukemia. 2017 Apr;31(4):997-1000. doi: 10.1038/leu.2017.5. Epub 2017 Jan 11.
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Improving the efficacy of proteasome inhibitors in the treatment of renal cell carcinoma by combination with the human immunodeficiency virus (HIV)-protease inhibitors lopinavir or nelfinavir.通过与人类免疫缺陷病毒（HIV）-蛋白酶抑制剂洛匹那韦或奈非那韦联合应用，提高蛋白酶体抑制剂治疗肾细胞癌的疗效。
BJU Int. 2018 Apr;121(4):600-609. doi: 10.1111/bju.14083. Epub 2017 Dec 10.
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Proteasome inhibitor-based therapy for treatment of newly diagnosed multiple myeloma.基于蛋白酶体抑制剂的治疗方案用于治疗新诊断的多发性骨髓瘤。
Semin Oncol. 2017 Dec;44(6):381-384. doi: 10.1053/j.seminoncol.2018.01.002. Epub 2018 Jan 12.

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Impact of proteostasis workload on sensitivity to proteasome inhibitors in multiple myeloma.蛋白质稳态工作负荷对多发性骨髓瘤中蛋白酶体抑制剂敏感性的影响
Clin Exp Med. 2025 May 26;25(1):176. doi: 10.1007/s10238-025-01713-z.
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Proteasome inhibition induces DNA methylation alteration by attenuating the synthesis of DNA methyltransferase 1 and 3B in colorectal cancer.蛋白酶体抑制通过减弱结直肠癌中DNA甲基转移酶1和3B的合成诱导DNA甲基化改变。
Sci Rep. 2025 Mar 12;15(1):8534. doi: 10.1038/s41598-025-92390-1.
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Different Strategies to Overcome Resistance to Proteasome Inhibitors-A Summary 20 Years after Their Introduction.克服蛋白酶体抑制剂耐药性的不同策略——引入 20 年后的总结。
Int J Mol Sci. 2024 Aug 16;25(16):8949. doi: 10.3390/ijms25168949.
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Antiretroviral Drug Repositioning for Glioblastoma.用于胶质母细胞瘤的抗逆转录病毒药物重新定位
Cancers (Basel). 2024 Apr 30;16(9):1754. doi: 10.3390/cancers16091754.
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An Open-Label Phase I Study of Metformin and Nelfinavir in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma.一项评估米哚妥林联合维奈托克治疗复发/难治性急性髓系白血病患者的安全性、耐受性、药代动力学和初步疗效的 I 期、开放性、剂量递增和扩展研究
Clin Lymphoma Myeloma Leuk. 2024 May;24(5):298-304. doi: 10.1016/j.clml.2024.01.002. Epub 2024 Jan 6.
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The cytotoxic activity of carfilzomib together with nelfinavir is superior to the bortezomib/nelfinavir combination in non-small cell lung carcinoma.卡非佐米联合奈非那韦的细胞毒性活性优于硼替佐米/奈非那韦联合在非小细胞肺癌中的应用。
Sci Rep. 2023 Mar 17;13(1):4411. doi: 10.1038/s41598-023-31400-6.
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Targeting the integrated stress response in hematologic malignancies.靶向血液系统恶性肿瘤中的综合应激反应
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The evolving role and utility of off-label drug use in multiple myeloma.多发性骨髓瘤中药物非适应证使用的角色演变及效用
Explor Target Antitumor Ther. 2021;2(4):355-373. doi: 10.37349/etat.2021.00050. Epub 2021 Aug 30.
9
Contribution of the Tumor Microenvironment to Metabolic Changes Triggering Resistance of Multiple Myeloma to Proteasome Inhibitors.肿瘤微环境对引发多发性骨髓瘤对蛋白酶体抑制剂耐药的代谢变化的作用。
Front Oncol. 2022 May 26;12:899272. doi: 10.3389/fonc.2022.899272. eCollection 2022.
10
The aspartyl protease DDI2 drives adaptation to proteasome inhibition in multiple myeloma.天冬氨酸蛋白酶 DDI2 驱动多发性骨髓瘤对蛋白酶体抑制的适应性。
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本文引用的文献

1
Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma.达雷妥尤单抗联合泊马度胺及地塞米松治疗复发和/或难治性多发性骨髓瘤
Blood. 2017 Aug 24;130(8):974-981. doi: 10.1182/blood-2017-05-785246. Epub 2017 Jun 21.
2
Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study.复发多发性骨髓瘤的自然史，对免疫调节剂和蛋白酶体抑制剂耐药：一项多中心 IMWG 研究。
Leukemia. 2017 Nov;31(11):2443-2448. doi: 10.1038/leu.2017.138. Epub 2017 May 12.
3
Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma.泊马度胺联合低剂量地塞米松在STRATUS（MM - 010）中的安全性和有效性：一项针对难治性多发性骨髓瘤的3b期研究
Blood. 2016 Jul 28;128(4):497-503. doi: 10.1182/blood-2016-02-700872. Epub 2016 May 25.
4
Proteasome inhibitor-adapted myeloma cells are largely independent from proteasome activity and show complex proteomic changes, in particular in redox and energy metabolism.蛋白酶体抑制剂适应性骨髓瘤细胞在很大程度上不依赖蛋白酶体活性，并显示出复杂的蛋白质组学变化，特别是在氧化还原和能量代谢方面。
Leukemia. 2016 Nov;30(11):2198-2207. doi: 10.1038/leu.2016.102. Epub 2016 Apr 27.
5
Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma.随机多中心 2 期研究：泊马度胺、环磷酰胺和地塞米松治疗复发/难治性骨髓瘤。
Blood. 2016 May 26;127(21):2561-8. doi: 10.1182/blood-2015-11-682518. Epub 2016 Mar 1.
6
Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial.达雷妥尤单抗单药治疗治疗难治性多发性骨髓瘤患者（SIRIUS）：一项开放标签、随机、2 期试验。
Lancet. 2016 Apr 9;387(10027):1551-1560. doi: 10.1016/S0140-6736(15)01120-4. Epub 2016 Jan 7.
7
Treatment with the HIV protease inhibitor nelfinavir triggers the unfolded protein response and may overcome proteasome inhibitor resistance of multiple myeloma in combination with bortezomib: a phase I trial (SAKK 65/08).使用HIV蛋白酶抑制剂奈非那韦进行治疗可引发未折叠蛋白反应，并且与硼替佐米联合使用时可能克服多发性骨髓瘤对蛋白酶体抑制剂的耐药性：一项I期试验（SAKK 65/08）。
Haematologica. 2016 Mar;101(3):346-55. doi: 10.3324/haematol.2015.135780. Epub 2015 Dec 11.
8
Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma.卡非佐米、泊马度胺和地塞米松用于复发或难治性骨髓瘤。
Blood. 2015 Nov 12;126(20):2284-90. doi: 10.1182/blood-2015-05-643320. Epub 2015 Sep 17.
9
Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.Daratumumab 单药治疗多发性骨髓瘤中针对 CD38。
N Engl J Med. 2015 Sep 24;373(13):1207-19. doi: 10.1056/NEJMoa1506348. Epub 2015 Aug 26.
10
Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study.来那度胺单药或联合低剂量地塞米松治疗复发/难治性多发性骨髓瘤的随机 2 期研究。
Blood. 2014 Mar 20;123(12):1826-32. doi: 10.1182/blood-2013-11-538835. Epub 2014 Jan 13.

Promising activity of nelfinavir-bortezomib-dexamethasone in proteasome inhibitor-refractory multiple myeloma.

作者信息

Driessen Christoph, Müller Rouven, Novak Urban, Cantoni Nathan, Betticher Daniel, Mach Nicolas, Rüfer Axel, Mey Ulrich, Samaras Panagiotis, Ribi Karin, Besse Lenka, Besse Andrej, Berset Catherine, Rondeau Stephanie, Hawle Hanne, Hitz Felicitas, Pabst Thomas, Zander Thilo

机构信息

Department of Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Department of Hematology and Oncology, University Hospital Zurich, Zurich, Switzerland.

出版信息

Blood. 2018 Nov 8;132(19):2097-2100. doi: 10.1182/blood-2018-05-851170. Epub 2018 Sep 20.

DOI:10.1182/blood-2018-05-851170
PMID:30237154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6238158/
Abstract
摘要