Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment

被引:32
|
作者
Yang, Huanjie [1 ]
Chen, Xin [2 ,3 ]
Li, Kai [1 ]
Cheaito, Hassan [4 ]
Yang, Qianqian [2 ,3 ]
Wu, Guojun [4 ]
Liu, Jinbao [2 ,3 ]
Dou, Q. Ping [2 ,3 ,4 ,5 ,6 ]
机构
[1] Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150001, Peoples R China
[2] Inst Guangzhou Med Univ, Guangzhou Municipal & Guangdong Prov Key Labrator, State Key Labrotory Resp Dis, Affiliated Canc Hosp, Guangzhou 510095, Peoples R China
[3] Inst Guangzhou Med Univ, Guangzhou 510095, Peoples R China
[4] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Sch Med, Dept Oncol, Detroit, MI 48201 USA
[5] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA
[6] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA
基金
中国国家自然科学基金; 美国国家卫生研究院;
关键词
Drug reposition; Protein degradation; Post-translational modification; UPS inhibitors; Cancer therapies; SMALL-MOLECULE INHIBITOR; CELLS IN-VITRO; NF-KAPPA-B; ANTIRHEUMATIC AGENT AURANOFIN; ENDOPLASMIC-RETICULUM STRESS; DISULFIRAM TARGETS CANCER; MULTIPLE-MYELOMA CELLS; II CLINICAL-TRIAL; DEUBIQUITINASE INHIBITOR; PHASE-II;
D O I
10.1016/j.semcancer.2019.12.013
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The ubiquitin-proteasome system (UPS) plays a central role in the degradation of cellular proteins. Targeting protein degradation has been validated as an effective strategy for cancer therapy since 2003. Several components of the UPS have been validated as potential anticancer targets, including 20S proteasomes, 19S proteasome-associated deubiquitinases (DUBs) and ubiquitin ligases (E3s). 20S proteasome inhibitors (such as bortezomib/BTZ and carfilzomib/CFZ) have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma (MM) and some other liquid tumors. Although survival of MM patients has been improved by the introduction of BTZ-based therapies, these clinical 20S proteasome inhibitors have several limitations, including emergence of resistance in MM patients, neuro-toxicities, and little efficacy in solid tumors. One of strategies to improve the current status of cancer treatment is to repurpose old drugs with UPS-inhibitory properties as new anticancer agents. Old drug reposition represents an attractive drug discovery approach compared to the traditional de novo drug discovery process which is time-consuming and costly. In this review, we summarize status of repurposed inhibitors of various UPS components, including 20S proteasomes, 19S -associated DUBs, and ubiquitin ligase E3s. The original and new mechanisms of action, molecular targets, and potential anticancer activities of these repurposed UPS inhibitors are reviewed, and their new uses including combinational therapies for cancer treatment are discussed.
引用
收藏
页码:105 / 122
页数:18
相关论文
共 50 条
  • [1] The ubiquitin-proteasome pathway and proteasome inhibitors
    Myung, J
    Kim, KB
    Crews, CM
    MEDICINAL RESEARCH REVIEWS, 2001, 21 (04) : 245 - 273
  • [2] The ubiquitin-proteasome pathway in cancer
    V Spataro
    C Norbury
    AL Harris
    British Journal of Cancer, 1998, 77 : 448 - 455
  • [3] The ubiquitin-proteasome pathway in cancer
    Spataro, V
    Norbury, C
    Harris, AL
    BRITISH JOURNAL OF CANCER, 1998, 77 (03) : 448 - 455
  • [4] The role of the ubiquitin-proteasome pathway in cancer development and treatment
    Ding, Fangbao
    Xiao, Haibo
    Wang, Mingsong
    Xie, Xiao
    Hu, Fengqing
    FRONTIERS IN BIOSCIENCE-LANDMARK, 2014, 19 : 886 - 895
  • [5] Ubiquitin-Proteasome Pathway and Prostate Cancer
    Chen, Fang-Zhi
    Zhao, Xiao-Kun
    ONKOLOGIE, 2013, 36 (10): : 592 - 596
  • [6] Natural Product Inhibitors of the Ubiquitin-Proteasome Pathway
    Schneekloth, John S., Jr.
    Crews, Craig M.
    CURRENT DRUG TARGETS, 2011, 12 (11) : 1581 - 1594
  • [7] Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing
    Soave, Claire L.
    Guerin, Tracey
    Liu, Jinbao
    Dou, Q. Ping
    CANCER AND METASTASIS REVIEWS, 2017, 36 (04) : 717 - 736
  • [8] Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing
    Claire L. Soave
    Tracey Guerin
    Jinbao Liu
    Q. Ping Dou
    Cancer and Metastasis Reviews, 2017, 36 : 717 - 736
  • [9] Ubiquitin-proteasome pathway
    Rivett, AJ
    CURRENT PROTEIN & PEPTIDE SCIENCE, 2004, 5 (03)
  • [10] The ubiquitin-proteasome pathway
    Roos-Mattjus, P
    Sistonen, L
    ANNALS OF MEDICINE, 2004, 36 (04) : 285 - 295