Progress in the resistance mechanisms of tumor cells to the neddylation inhibitor MLN4924 and its countermeasures

doi:10.3877/cma.j.issn.2095-1221.2026.02.003

Abstract

Abstract:

The neddylation process covalently conjugates neural precursor cell expressed developmentally downregulated 8 (NEDD8) to substrate proteins through a continuous enzymatic cascade reaction, which affects the stability, conformation, and function of substrate proteins, thereby regulating numerous downstream biological processes. The neddylation process is associated with the progression and prognosis of various types of tumors. As the only currently known activating enzyme in the neddylation process, NEDD8-activating enzyme (NAE) is an important target for the development of anti-cancer drugs. MLN4924, a selective NAE inhibitor, has good therapeutic effects on various types of solid tumors and hematological malignancies. Currently, 41 clinical trials have entered phases Ⅱ/Ⅲ, indicating promising application prospects. The drug resistance of tumor cells is an important cause of treatment failure in cancer patients. Once tumor cells acquire drug resistance, it will significantly affect the prognosis of patients. This article reviews the current research progress on the resistance mechanism of MLN4924 and the measures to address the problem of resistance to it.

Key words: MLN4924, Neddylation, Drug resistance mechanism, Combination drug therapy, Tumor cells

Lei Xing, Yu Bu, Minghua Zhang, Jiao Fan. Progress in the resistance mechanisms of tumor cells to the neddylation inhibitor MLN4924 and its countermeasures[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2026, 16(02): 86-93.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhxbygxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-1221.2026.02.003

https://zhxbygxbzz.cma-cmc.com.cn/EN/Y2026/V16/I02/86

Figures/Tables 2

References 74

1	El-Tanani M, Rabbani SA, Babiker R, et al. Unraveling the tumor microenvironment: insights into cancer metastasis and therapeutic strategies[J]. Cancer Lett, 2024, 591:216894.
2	Schröter F, Adjaye J. The proteasome complex and the maintenance of pluripotency: sustain the fate by mopping up?[J]. Stem Cell Res Ther, 2014, 5(1):24.
3	Sun Y, Baechler SA, Zhang X, et al. Targeting neddylation sensitizes colorectal cancer to topoisomerase Ⅰ inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex[J]. Nat Commun, 2023, 14(1):3762.
4	Reinstein E, Ciechanover A. Narrative review: protein degradation and human diseases: the ubiquitin connection[J]. Ann Intern Med, 2006, 145(9):676-684.
5	Hershko A. The ubiquitin system for protein degradation and some of its roles in the control of the cell-division cycle (Nobel lecture)[J]. Angew Chem Int Ed Engl, 2005, 44(37):5932-5943.
6	Kamitani T, Kito K, Nguyen HP, et al. Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein[J]. J Biol Chem, 1997, 272(45):28557-28562.
7	Pan ZQ, Kentsis A, Dias DC, et al. Nedd8 on cullin: building an expressway to protein destruction[J]. Oncogene, 2004, 23(11):1985-1997.
8	Whitby FG, Xia G, Pickart CM, et al. Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes[J]. J Biol Chem, 1998, 273(52):34983-34991.
9	Bohnsack RN, Haas AL. Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer[J]. J Biol Chem, 2003, 278(29):26823-26830.
10	Jones J, Wu K, Yang Y, et al. A targeted proteomic analysis of the ubiquitin-like modifier nedd8 and associated proteins[J]. J Proteome Res, 2008, 7(3):1274-1287.
11	Ni S, Chen X, Yu Q, et al. Discovery of candesartan cilexetic as a novel neddylation inhibitor for suppressing tumor growth[J]. Eur J Med Chem, 2020, 185:111848.
12	Stuber K, Schneider T, Werner J, et al. Structural and functional consequences of NEDD8 phosphorylation[J]. Nat Commun, 2021, 12(1):5939.
13	Castagnoli L, Mandaliti W, Nepravishta R, et al. Selectivity of the CUBAN domain in the recognition of ubiquitin and NEDD8[J]. FEBS J, 2019, 286(4):653-677.
14	Schwechheimer C. NEDD8-its role in the regulation of Cullin-RING ligases[J]. Curr Opin Plant Biol, 2018, 45(Pt A):112-119.
15	Mohanty P, Chatterjee KS, Das R. NEDD8 deamidation inhibits Cullin RING ligase dynamics[J]. Front Immunol, 2021, 12:695331.
16	Baek K, Krist DT, Prabu JR, et al. NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly[J]. Nature, 2020, 578(7795):461-466.
17	Ribet D, Cossart P. Ubiquitin, SUMO, and NEDD8: key targets of bacterial pathogens[J]. Trends Cell Biol, 2018, 28(11):926-940.
18	Kostrhon S, Prabu JR, Baek K, et al. CUL5-ARIH2 E3-E3 ubiquitin ligase structure reveals cullin-specific NEDD8 activation[J]. Nat Chem Biol, 2021, 17(10):1075-1083.
19	Zhao B, Zhang K, Villhauer EB, et al. Phage display to identify Nedd8-mimicking peptides as inhibitors of the Nedd8 transfer cascade[J]. Chembiochem, 2013, 14(11):1323-1330.
20	Watson IR, Irwin MS, Ohh M. NEDD8 pathways in cancer, Sine Quibus Non[J]. Cancer Cell, 2011, 19(2):168-176.
21	Schmidt MHH, Dikic I. Ubiquitin and NEDD8: brothers in arms[J]. Sci STKE, 2006, 2006(362):pe50.
22	Assumpção A, Lu Z, Marlowe K W, et al. Targeting NEDD8-activating enzyme is a new approach to treat canine diffuse large B-cell lymphoma[J]. Vet Comp Oncol, 2018, 16(4):606-615.
23	Li L, Kang J, Zhang W, et al. Validation of NEDD8-conjugating enzyme UBC12 as a new therapeutic target in lung cancer[J]. EBioMedicine, 2019, 45:81-91.
24	Wang S, Xian J, Li L, et al. NEDD8-conjugating enzyme UBC12 as a novel therapeutic target in esophageal squamous cell carcinoma[J]. Signal Transduct Target Ther, 2020, 5(1):123.
25	Huang DT, Paydar A, Zhuang M, et al. Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1[J]. Mol Cell, 2005, 17(3):341-350.
26	Zhou W, Xu J, Tan M, et al. UBE2M is a stress-inducible dual E2 for neddylation and ubiquitylation that promotes targeted degradation of UBE2F[J]. Mol Cell, 2018, 70(6):1008-1024.e1006.
27	Zhou L, Lin X, Zhu J, et al. NEDD8-conjugating enzyme E2s: critical targets for cancer therapy[J]. Cell Death Discov, 2023, 9(1):23.
28	Zheng YC, Guo YJ, Wang B, et al. Targeting neddylation E2s: a novel therapeutic strategy in cancer[J]. J Hematol Oncol, 2021, 14(1):57.
29	Chew EH, Hagen T. Substrate-mediated regulation of cullin neddylation[J]. J Biol Chem, 2007, 282(23):17032-17040.
30	Zhou H, Lu J, Liu L, et al. A potent small-molecule inhibitor of the DCN1-UBC12 interaction that selectively blocks cullin 3 neddylation[J]. Nat Commun, 2017, 8(1):1150.
31	Scott DC, Sviderskiy VO, Monda JK, et al. Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8[J]. Cell, 2014, 157(7):1671-1684.
32	Hori T, Osaka F, Chiba T, et al. Covalent modification of all members of human cullin family proteins by NEDD8[J]. Oncogene, 1999, 18(48):6829-6834.
33	Mergner J, Schwechheimer C. The NEDD8 modification pathway in plants[J]. Front Plant Sci, 2014, 5:103.
34	Bano I, Malhi M, Zhao M, et al. A review on cullin neddylation and strategies to identify its inhibitors for cancer therapy[J]. 3 Biotech, 2022, 12(4):103.
35	Li Y, Wang C, Xu T, et al. Discovery of a small molecule inhibitor of cullin neddylation that triggers ER stress to induce autophagy[J]. Acta Pharm Sin B, 2021, 11(11):3567-3584.
36	Zhong HJ, Yang H, Chan DS, et al. A metal-based inhibitor of NEDD8-activating enzyme[J]. PLoS One, 2012, 7(11):e49574.
37	Xu GW, Toth JI, Da Silva SR, et al. Mutations in UBA3 confer resistance to the NEDD8-activating enzyme inhibitor MLN4924 in human leukemic cells[J]. PLoS One, 2014, 9(4):e93530.
38	Hong X, Li S, Li W, et al. Disruption of protein neddylation with MLN4924 attenuates paclitaxel-induced apoptosis and microtubule polymerization in ovarian cancer cells[J]. Biochem Biophys Res Commun, 2019, 508(3):986-990.
39	Jiang Y, Cheng W, Li L, et al. Effective targeting of the ubiquitin-like modifier NEDD8 for lung adenocarcinoma treatment[J]. Cell Biol Toxicol, 2020, 36(4):349-364.
40	Chen Y, Du M, Yusuying S, et al. Nedd8-activating enzyme inhibitor MLN4924 (Pevonedistat), inhibits miR-1303 to suppress human breast cancer cell proliferation via targeting p27(Kip1)[J]. Exp Cell Res, 2020, 392(2): 112038.
41	Faessel HM, Mould DR, Zhou X, et al. Population pharmacokinetics of pevonedistat alone or in combination with standard of care in patients with solid tumours or haematological malignancies[J]. Br J Clin Pharmacol, 2019, 85(11):2568-2579.
42	Swords RT, Coutre S, Maris MB, et al. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML[J]. Blood, 2018, 131(13):1415-1424.
43	Swords RT, Watts J, Erba HP, et al. Expanded safety analysis of pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukemia and myelodysplastic syndromes[J]. Blood Cancer J, 2017, 7(2):e520.
44	Ochiiwa H, Ailiken G, Yokoyama M, et al. TAS4464, a NEDD8-activating enzyme inhibitor, activates both intrinsic and extrinsic apoptotic pathways via c-Myc-mediated regulation in acute myeloid leukemia[J]. Oncogene, 2021, 40(7):1217-1230.
45	Locarnini S. Primary resistance, multidrug resistance, and cross-resistance pathways in HBV as a consequence of treatment failure[J]. Hepatol Int, 2008, 2(2):147-151.
46	Soragni A, Knudsen ES, O'connor TN, et al. Acquired resistance in cancer: towards targeted therapeutic strategies[J]. Nat Rev Cancer, 2025, 25(8):613-633.
47	Milhollen MA, Thomas MP, Narayanan U, et al. Treatment-emergent mutations in NAEβ confer resistance to the NEDD8-activating enzyme inhibitor MLN4924[J]. Cancer Cell, 2012, 21(3):388-401.
48	Kathawala RJ, Espitia CM, Jones TM, et al. ABCG2 Overexpression Contributes to Pevonedistat Resistance[J]. Cancers (Basel), 2020, 12(2):429.
49	Zhang H, He P, Zhou Q, et al. The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells [J]. Cancer Cell Int, 2021, 21(1):369.
50	Ajaz M, Jefferies S, Brazil L, et al. Current and investigational drug strategies for glioblastoma[J]. Clin Oncol (R Coll Radiol), 2014, 26(7):419-430.
51	Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations[J]. Sci Transl Med, 2016, 8(328):328rv324.
52	Roth P, Valavanis A, Weller M. Long-term control and partial remission after initial pseudoprogression of glioblastoma by anti-PD-1 treatment with nivolumab[J]. Neuro Oncol, 2017, 19(3):454-456.
53	Nduom EK, Wei J, Yaghi NK, et al. PD-L1 expression and prognostic impact in glioblastoma[J]. Neuro Oncol, 2016, 18(2):195-205.
54	Kong W, He L, Coppola M, et al. MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer[J]. J Biol Chem, 2016, 291(43):22855.
55	Marcucci G, Maharry KS, Metzeler KH, et al. Clinical role of microRNAs in cytogenetically normal acute myeloid leukemia: miR-155 upregulation independently identifies high-risk patients[J]. J Clin Oncol, 2013, 31(17):2086-2093.
56	Khalife J, Radomska HS, Santhanam R, et al. Pharmacological targeting of miR-155 via the NEDD8-activating enzyme inhibitor MLN4924 (Pevonedistat) in FLT3-ITD acute myeloid leukemia[J]. Leukemia, 2015, 29(10):1981-1992.
57	Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor[J]. Nat Rev Mol Cell Biol, 2012, 13(5):283-296.
58	Taylor B, Tang N, Hao Y, et al. Glioblastoma vulnerability to neddylation inhibition is dependent on PTEN status, and dysregulation of the cell cycle and DNA replication[J]. Neurooncol Adv, 2024, 6(1):vdae104.
59	Soucy TA, Dick LR, Smith PG, et al. The NEDD8 conjugation pathway and its relevance in cancer biology and therapy[J]. Genes Cancer, 2010, 1(7):708-716.
60	Zhou L, Zhang W, Sun Y, et al. Protein neddylation and its alterations in human cancers for targeted therapy[J]. Cell Signal, 2018, 44:92-102.
61	Chen X, Cui D, Bi Y, et al. AKT inhibitor MK-2206 sensitizes breast cancer cells to MLN4924, a first-in-class NEDD8-activating enzyme (NAE) inhibitor[J]. Cell Cycle, 2018, 17(16):2069-2079.
62	Guo Y, Hu Z, Bai L, et al. Increased glucose utilization is a targetable vulnerability to overcome drug resistance associated with neddylation blockade[J]. Biochem Pharmacol, 2025, 236:116905.
63	Zhou L, Chen S, Zhang Y, et al. The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR[J]. Blood, 2016, 127(18):2219-2230.
64	Salaroglio IC, Belisario DC, Bironzo P, et al. SKP2 drives the sensitivity to neddylation inhibitors and cisplatin in malignant pleural mesothelioma[J]. J Exp Clin Cancer Res, 2022, 41(1):75.
65	Glaser SP, Lee EF, Trounson E, et al. Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia[J]. Genes Dev, 2012, 26(2):120-125.
66	Zhang B, Gojo I, Fenton RG. Myeloid cell factor-1 is a critical survival factor for multiple myeloma[J]. Blood, 2002, 99(6):1885-1893.
67	Van Delft MF, Wei AH, Mason KD, et al. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized[J]. Cancer Cell, 2006, 10(5):389-399.
68	Knorr KL, Schneider PA, Meng XW, et al. MLN4924 induces Noxa upregulation in acute myelogenous leukemia and synergizes with Bcl-2 inhibitors[J]. Cell Death Differ, 2015, 22(12):2133-2142.
69	Pan R, Hogdal LJ, Benito JM, et al. Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia[J]. Cancer Discov, 2014, 4(3):362-375.
70	Zhang S, You X, Xu T, et al. PD-L1 induction via the MEK-JNK-AP1 axis by a neddylation inhibitor promotes cancer-associated immunosuppression[J]. Cell Death Dis, 2022, 13(10):844.
71	Foster JH, Reid JM, Minard C, et al. Phase 1 study of NEDD8 activating enzyme inhibitor pevonedistat in combination with chemotherapy in pediatric patients with recurrent or refractory solid tumors (ADVL1615)[J]. Eur J Cancer, 2024, 209:114241.
72	Shoji H, Takahari D, Ooki A, et al. Phase I study of pevonedistat combined with capecitabine and oxaliplatin in patients with platinum-refractory advanced gastric cancer[J]. Sci Rep, 2025, 16(1):692.
73	Short NJ, Muftuoglu M, Ong F, et al. A phase 1/2 study of azacitidine, venetoclax and pevonedistat in newly diagnosed secondary AML and in MDS or CMML after failure of hypomethylating agents[J]. J Hematol Oncol, 2023, 16(1):73.
74	Murthy GSG, Saliba AN, Szabo A, et al. A phase Ⅰ study of pevonedistat, azacitidine, and venetoclax in patients with relapsed/refractory acute myeloid leukemia[J]. Haematologica, 2024, 109(9):2864-2872.

试验编号	涉及药物	治疗疾病	试验分期	治疗效果
NCT01415765	MLN4924/Etoposide/Prednisone/Vincristine/Cyclophosphamide/Doxorubicin/Rituximab	弥漫大B细胞淋巴瘤	Ⅰ期/Ⅱ期	未公布
NCT01011530	MLN4924	黑色素瘤	Ⅰ期	未公布
NCT00677170	MLN4924	非血液系统恶性肿瘤	Ⅰ期	未公布
NCT02122770	MLN4924/Fluconazole/Itraconazole/Docetaxel/Carboplatin/Paclitaxel	晚期实体肿瘤	Ⅰ期	缓解者占比：22.2%
NCT03813147	Azacitidine/Cytarabine/Fludarabine Phosphate/Methotrexate/MLN4924	急性髓系白血病骨髓增生异常综合征	Ⅰ期	缓解者占比：33.3%
NCT01814826	MLN4924/Azacitidine	急性粒细胞白血病	Ⅰ期	完全缓解：43% 部分缓解：14%
NCT00722488	MLN4924	淋巴瘤/多发性骨髓瘤	Ⅰ期	未公布
NCT00911066	MLN4924/Azacitidine	急性粒细胞白血病骨髓增生异常综合征急性淋巴细胞白血病	Ⅰ期	未公布
NCT01862328	MLN4924/Paclitaxel/Gemcitabine/Docetaxel/Carboplatin	实体肿瘤	Ⅰ期	完全缓解：0 部分缓解：19%
NCT03772925	Belinostat/MLN4924	急性髓系白血病骨髓增生异常综合征	Ⅰ期	未公布
NCT03745352	Azacitidine/MLN4924	急性髓系白血病	Ⅱ期	未公布
NCT03965689	Carboplatin/Paclitaxel/MLN4924	非小细胞肺癌	Ⅱ期	完全缓解：0 部分缓解：16%
NCT03770260	Ixazomib Citrate/MLN4924	多发性骨髓瘤	Ⅰ期	未分析
NCT04800627	Pembrolizumab/MLN4924	晚期实体肿瘤	Ⅰ期/Ⅱ期	未分析
NCT03479268	Ibrutinib/MLN4924	难治性慢性淋巴细胞白血病	Ⅰ期	未公布
NCT03330821	Cytarabine/Idarubicin/MLN4924	急性髓系白血病	Ⅰ期/Ⅱ期	未公布
NCT04172844	Azacitidine/Venetoclax/MLN4924	急性粒细胞白血病	Ⅰ期	未公布
NCT03009240	Decitabine/MLN4924	急性髓系白血病	Ⅰ期	未公布
NCT03323034	Irinotecan/MLN4924/Temozolomide	难治性实体肿瘤或淋巴瘤	Ⅰ期	缓解者占比：16.7%
NCT03862157	Azacitidine/MLN4924/Venetoclax	急性髓系白血病	Ⅰ期/Ⅱ期	未公布
NCT03459859	MLN4924/Cytarabine	骨髓增生异常综合征	Ⅰ期	未公布
NCT03386214	MLN4924/Ruxolitinib	骨髓纤维化	Ⅰ期	未公布
NCT03330106	MLN4924/Docetaxel/Carboplatin/Paclitaxe	晚期实体肿瘤	Ⅰ期	缓解者占比：9.1%
NCT03709576	MLN4924/Azacitidine	急性髓系白血病	Ⅱ期	未分析
NCT02782468	MLN4924/Azacitidine	骨髓增生异常综合征	Ⅰ期	缓解者占比：100%
NCT03486314	MLN4924/Rifampin/Docetaxel/Carboplatin/Paclitaxel	晚期实体肿瘤	Ⅰ期	完全缓解：0 部分缓解：33.3%
NCT03057366	MLN4924/Docetaxel/Carboplatin/Paclitaxel	晚期实体肿瘤	Ⅰ期	缓解者占比：0
NCT03349281	MLN4924/Vincristine/Dexamethasone/PEG-asparaginase/Doxorubicin/Cytarabine/Methotrexate/Hydrocortisone	难治性急性淋巴细胞白血病非霍奇金淋巴瘤	Ⅰ期	未公布
NCT03814005	Azacitidine/MLN4924	血液系统恶性肿瘤	Ⅰ期	缓解者占比：50%
NCT04266795	MLN4924/Venetoclax/Azacitidine	急性髓系白血病	Ⅱ期	未公布
NCT04175912	Carboplatin/Paclitaxel/MLN4924	肝内胆管癌	Ⅱ期	无治疗效果
NCT03013998	MLN4924	急性髓系白血病	Ⅰ期/Ⅱ期	未公布
NCT04712942	MLN4924/Azacitidine	骨髓增生异常综合征	Ⅱ期	未公布
NCT03319537	MLN4924/Pemetrexed cisplatin	间皮瘤	Ⅰ期/Ⅱ期	缓解者占比：22.2%
NCT04090736	MLN4924/Azacitidine	急性髓系白血病	Ⅲ期	未公布
NCT04985656	MLN4924/Decitabine/Cedazuridine	高危骨髓增生异常综合征	Ⅱ期	未公布
NCT03228186	MLN4924/Docetaxel	晚期非小细胞肺癌	Ⅱ期	缓解者占比：22%
NCT04484363	MLN4924/Azacitidine	骨髓增生异常综合征	未注明	未公布
NCT03268954	Azacitidine/MLN4924	骨髓增生异常综合征	Ⅲ期	缓解者占比：56.3%
NCT02610777	Azacitidine/MLN4924	骨髓增生异常综合征/白血病	Ⅱ期	缓解者占比：71%
NCT03238248	Azacitidine/MLN4924	骨髓增生异常综合征	Ⅱ期	缓解者占比：23.9%

试验编号	涉及药物	治疗疾病	试验分期	治疗效果
NCT01415765	MLN4924/Etoposide/Prednisone/Vincristine/Cyclophosphamide/Doxorubicin/Rituximab	弥漫大B细胞淋巴瘤	Ⅰ期/Ⅱ期	未公布
NCT01011530	MLN4924	黑色素瘤	Ⅰ期	未公布
NCT00677170	MLN4924	非血液系统恶性肿瘤	Ⅰ期	未公布
NCT02122770	MLN4924/Fluconazole/Itraconazole/Docetaxel/Carboplatin/Paclitaxel	晚期实体肿瘤	Ⅰ期	缓解者占比：22.2%
NCT03813147	Azacitidine/Cytarabine/Fludarabine Phosphate/Methotrexate/MLN4924	急性髓系白血病骨髓增生异常综合征	Ⅰ期	缓解者占比：33.3%
NCT01814826	MLN4924/Azacitidine	急性粒细胞白血病	Ⅰ期	完全缓解：43% 部分缓解：14%
NCT00722488	MLN4924	淋巴瘤/多发性骨髓瘤	Ⅰ期	未公布
NCT00911066	MLN4924/Azacitidine	急性粒细胞白血病骨髓增生异常综合征急性淋巴细胞白血病	Ⅰ期	未公布
NCT01862328	MLN4924/Paclitaxel/Gemcitabine/Docetaxel/Carboplatin	实体肿瘤	Ⅰ期	完全缓解：0 部分缓解：19%
NCT03772925	Belinostat/MLN4924	急性髓系白血病骨髓增生异常综合征	Ⅰ期	未公布
NCT03745352	Azacitidine/MLN4924	急性髓系白血病	Ⅱ期	未公布
NCT03965689	Carboplatin/Paclitaxel/MLN4924	非小细胞肺癌	Ⅱ期	完全缓解：0 部分缓解：16%
NCT03770260	Ixazomib Citrate/MLN4924	多发性骨髓瘤	Ⅰ期	未分析
NCT04800627	Pembrolizumab/MLN4924	晚期实体肿瘤	Ⅰ期/Ⅱ期	未分析
NCT03479268	Ibrutinib/MLN4924	难治性慢性淋巴细胞白血病	Ⅰ期	未公布
NCT03330821	Cytarabine/Idarubicin/MLN4924	急性髓系白血病	Ⅰ期/Ⅱ期	未公布
NCT04172844	Azacitidine/Venetoclax/MLN4924	急性粒细胞白血病	Ⅰ期	未公布
NCT03009240	Decitabine/MLN4924	急性髓系白血病	Ⅰ期	未公布
NCT03323034	Irinotecan/MLN4924/Temozolomide	难治性实体肿瘤或淋巴瘤	Ⅰ期	缓解者占比：16.7%
NCT03862157	Azacitidine/MLN4924/Venetoclax	急性髓系白血病	Ⅰ期/Ⅱ期	未公布
NCT03459859	MLN4924/Cytarabine	骨髓增生异常综合征	Ⅰ期	未公布
NCT03386214	MLN4924/Ruxolitinib	骨髓纤维化	Ⅰ期	未公布
NCT03330106	MLN4924/Docetaxel/Carboplatin/Paclitaxe	晚期实体肿瘤	Ⅰ期	缓解者占比：9.1%
NCT03709576	MLN4924/Azacitidine	急性髓系白血病	Ⅱ期	未分析
NCT02782468	MLN4924/Azacitidine	骨髓增生异常综合征	Ⅰ期	缓解者占比：100%
NCT03486314	MLN4924/Rifampin/Docetaxel/Carboplatin/Paclitaxel	晚期实体肿瘤	Ⅰ期	完全缓解：0 部分缓解：33.3%
NCT03057366	MLN4924/Docetaxel/Carboplatin/Paclitaxel	晚期实体肿瘤	Ⅰ期	缓解者占比：0
NCT03349281	MLN4924/Vincristine/Dexamethasone/PEG-asparaginase/Doxorubicin/Cytarabine/Methotrexate/Hydrocortisone	难治性急性淋巴细胞白血病非霍奇金淋巴瘤	Ⅰ期	未公布
NCT03814005	Azacitidine/MLN4924	血液系统恶性肿瘤	Ⅰ期	缓解者占比：50%
NCT04266795	MLN4924/Venetoclax/Azacitidine	急性髓系白血病	Ⅱ期	未公布
NCT04175912	Carboplatin/Paclitaxel/MLN4924	肝内胆管癌	Ⅱ期	无治疗效果
NCT03013998	MLN4924	急性髓系白血病	Ⅰ期/Ⅱ期	未公布
NCT04712942	MLN4924/Azacitidine	骨髓增生异常综合征	Ⅱ期	未公布
NCT03319537	MLN4924/Pemetrexed cisplatin	间皮瘤	Ⅰ期/Ⅱ期	缓解者占比：22.2%
NCT04090736	MLN4924/Azacitidine	急性髓系白血病	Ⅲ期	未公布
NCT04985656	MLN4924/Decitabine/Cedazuridine	高危骨髓增生异常综合征	Ⅱ期	未公布
NCT03228186	MLN4924/Docetaxel	晚期非小细胞肺癌	Ⅱ期	缓解者占比：22%
NCT04484363	MLN4924/Azacitidine	骨髓增生异常综合征	未注明	未公布
NCT03268954	Azacitidine/MLN4924	骨髓增生异常综合征	Ⅲ期	缓解者占比：56.3%
NCT02610777	Azacitidine/MLN4924	骨髓增生异常综合征/白血病	Ⅱ期	缓解者占比：71%
NCT03238248	Azacitidine/MLN4924	骨髓增生异常综合征	Ⅱ期	缓解者占比：23.9%

[1]	Hua Zhang, Yu Sun, Shijian Xiang, Yingmei Li, Xiaoqun Wang. Research on chemosensitivity evaluation using circulating tumor cells in advanced gastrointestinal cancer [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(06): 422-425.
[2]	Xueyuan Feng, Mengmeng Han, Ning Ma. Detection of circulating tumor cells and its application in breast cancer [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(03): 231-236.
[3]	Yongzhu He, Shaowei Ye, Liwen Liu, Junlin Qian, Kun He, Ruiqin Huang, Peng Peng, Qijie Luo, Zemin Hu. Predictive value of preoperative circulating tumor cells on recurrence of hepatocellular carcinoma after radiofrequency ablation [J]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(02): 137-141.
[4]	Ruifang Li, Mingshuai Wang, Nianzeng Xing. Advances in the application of circulating tumor cells in the diagnosis and prognosis of bladder cancer [J]. Chinese Journal of Endourology(Electronic Edition), 2025, 19(06): 705-713.
[5]	Wanhua Wu, Yiming Lai, Huiyang Fan, Zhenghui Guo, Hai Huang. Circulating tumor cells undergoing emt or expressing MAP1S help diagnosis of distant metastasis of prostate cancer [J]. Chinese Journal of Endourology(Electronic Edition), 2021, 15(05): 373-377.
[6]	Lei Xing, Jingqi Shi, Rongyan Li, Jing Liu, Jianwei Liu, Ling Ye, Minghua Zhang, Jiao Fan. Mechanisms of drug resistance to the neddylation inhibitor MLN4924 in NCI-H460 cells based on transcriptome sequencing analysis [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(01): 1-10.
[7]	Zhiguo Wang, Youzhi Wang, Changbao Xu, Changwei Liu, bin Hao. Prediction effect of ultrasound-guided prostate puncture combined with circulation tumor cells enumeration on prognosis of prostate cancer [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2019, 09(06): 327-332.
[8]	Guolei Li, Yingying Lou, Hao Feng, Weixue Zhang, Lihui Jia, Qian Yang. Establishment of a CTC sorting system for colorectal cancer and study of its consistency with tissue gene mutations [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2025, 14(03): 266-272.
[9]	Chao Fang, Zongguang Zhou. The detection methods and clinical applications of circulation tumor cells [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2019, 08(05): 501-504.
[10]	Yanwei Yang, Yanhong Liu. The application of liquid biopsy in common tumors [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2017, 06(02): 135-138.
[11]	Lijuan Yang, Xianghua Yin. Tumor markers for ovarian cancer: basic research and clinical applications [J]. Chinese Journal of Clinicians(Electronic Edition), 2017, 11(18): 2249-2252.
[12]	Shuxian Wen, Dannyu Zhou, Yunjian Xu, Liping Liu, Jun Gao. Application value of folate receptor-positive circulating tumor cells detection in the diagnosis and surgical effect evaluation of early pulmonary adenocarcinoma [J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2021, 09(04): 193-199.
[13]	Yujie Wang, Xia Guo, Xiaofei Wang. Detection methods and clinical applications of circulating tumor cells in breast cancer [J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2017, 05(02): 78-80.
[14]	Ruirong Li, Xueping Cui. Research advance of drug resistance mechanism of Klebsiella pneumonia [J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2016, 04(02): 86-90.
[15]	Enqiang Linghu. Revisiting solid tumor resection from a super minimally invasive perspective: A new lens on systemic and dynamic concepts [J]. Chinese Journal of Gastrointestinal Endoscopy(Electronic Edition), 2025, 12(04): 217-219.

Please choose a citation manager

Content to export