Abstract：
: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.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
Yang H,Chen X,Li K,Cheaito H,Yang Q,Wu G,Liu J,Dou QPdoi
10.1016/j.semcancer.2019.12.013subject
Has Abstractpub_date
2019-12-26 00:00:00eissn
1044-579Xissn
1096-3650pii
S1044-579X(19)30411-0pub_type
杂志文章,评审abstract：:The discovery of microRNAs (miRNAs) is one of the major scientific breakthroughs in recent years and has revolutionized the way we look at gene regulation. Although we are still at a very early stage in understanding their impact on immunity, miRNAs are changing the way we think about the development of the immune sys...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2008.01.005
更新日期：2008-04-01 00:00:00
abstract：:Tumor-stromal interactions induce expression of matrix metalloproteinases and serine proteases and, as shown recently, the cysteine protease cathepsin B. We speculate that such interactions upregulate the transcription factor Ets1, resulting in increased cathepsin B expression. This would be consistent with the observ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2004.08.001
更新日期：2005-04-01 00:00:00
abstract：:The anaphase promoting complex/ cyclosome (APC/C), is an evolutionarily conserved protein complex essential for cellular division due to its role in regulating the mitotic transition from metaphase to anaphase. In this review, we highlight recent work that has shed light on our understanding of the role of APC/C coact...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.03.001
更新日期：2020-12-01 00:00:00
abstract：:Hepatocellular carcinoma (HCC) is among the most frequently occurring cancers and the leading causes of cancer mortality worldwide. Identification of the signaling pathways regulating liver carcinogenesis is critical in developing novel chemoprevention and targeted therapies. Mitogen-activated protein kinases (MAPKs),...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.10.011
更新日期：2011-02-01 00:00:00
abstract：:Interferons are important cytokines which regulate antiviral, cell growth, immune modulatory and anti-tumor functions. These pleiotropic effects of interferons are brought about by a large number of cellular proteins, the interferon-inducible proteins. Investigation of the biochemical and cellular activities of some o...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2000.0312
更新日期：2000-04-01 00:00:00
abstract：:The key molecule for normal B cells is the surface Ig (sIg) of the B-cell receptor, which influences cell behaviour, even after neoplastic transformation. During B-cell maturation, sIg accumulates somatic mutations in the Ig variable region (V) genes and tumours retain these patterns, thereby revealing the point of di...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.08.004
更新日期：2010-12-01 00:00:00
abstract：:Mucins are large molecular weight glycoproteins characterized by carbohydrate sugars attached via 'O-glycosidic' linkages to serine or threonine. Mucins are synthesized by a variety of epithelial tissues as membrane-bound or secreted proteins, encoded by several distinct mucin genes. Numerous alterations of mucin-asso...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1991-12-01 00:00:00
abstract：:In this short review, we will give an overview of the various genes that can be activated by insertion of proviral DNA of the mouse mammary tumor virus during the formation of mammary cancer. These genes fall within three families: Wnt genes, FGF genes and Notch-related genes. We will summarize our current understandi...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1995.0018
更新日期：1995-06-01 00:00:00
abstract：:The 7th edition of the TNM defines multifocal breast cancer as multiple simultaneous ipsilateral and synchronous breast cancer lesions, provided they are macroscopically distinct and measurable using current traditional pathological and clinical tools. According to the College of American Pathologists (CAP), the chara...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2014.07.002
更新日期：2015-04-01 00:00:00
abstract：:Natural killer (NK) cells have important functions in the innate immunity to tumors. Recognition of tumor cells by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with ligands expressed on the tumor target. In addition, NK cell-target cell interactions require the engagement of a...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2006.07.002
更新日期：2006-10-01 00:00:00
abstract：:The molecular events underlying prostatic tumorigenesis remain incompletely understood. The application of cytogenetic, molecular genetic and molecular cytogenetic techniques have led to the identification of consistent genetic changes. This paper will discuss these techniques, review the genetic aberrations discovere...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.1997.0051
更新日期：1997-02-01 00:00:00
abstract：:Gynaecological carcinosarcomas are the most lethal gynaecological malignancies that are often highly resistant to standard chemotherapy. They are composed of both carcinomatous and sarcomatous components and are associated with high rates of metastatic disease. Due to their rarity, molecular studies have been carried ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.10.006
更新日期：2020-04-01 00:00:00
abstract：:Histamine is produced from histidine by histidine decarboxylase (HDC) in many cells including normal and malignant lymphocytes. We examined the expression of HDC and the effect of histamine receptor antagonists on the proliferation of a human T cell line, Jurkat and on antigen-driven proliferation of lymphocytes from ...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1006/scbi.2000.0306
更新日期：2000-02-01 00:00:00
abstract：:Dysfunction of the TP53 (p53) gene occurs in most if not all human malignancies. Two principal mechanisms are responsible for this dysfunction; mutation and downregulation of wild-type p53 mediated by MDM2/MDM4. Because of its almost universal inactivation in malignancy, p53 is a highly attractive target for the devel...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.07.005
更新日期：2020-07-31 00:00:00
abstract：:While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2017.03.004
更新日期：2017-04-01 00:00:00
abstract：:The dysregulation of apoptosis is a key step in developing cancers, and mediates resistance to cancer therapy. Commitment to apoptosis is caused by permeabilization of the outer mitochondrial membrane, a process regulated by the interactions between different proteins of Bcl-2 family. Furthermore, Bcl-2 family protein...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2013.08.008
更新日期：2013-12-01 00:00:00
abstract：:Growing evidence supports the notion that pharmaceutical targeting of the 5-hydroxytryptamine (5-HT) and dopamine (DA) systems offers the potential to treat human immune system disorders. This review describes this emerging area of research, which has the benefit of being supported by a relatively detailed understandi...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2007.12.007
更新日期：2008-06-01 00:00:00
abstract：:The tumor microenvironment (TME) is a complex meshwork of extracellular matrix (ECM) macromolecules filled with a collection of cells including cancer-associated fibroblasts (CAFs), blood vessel associated smooth muscle cells, pericytes, endothelial cells, mesenchymal stem cells and a variety of immune cells. In tumor...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.08.004
更新日期：2020-05-01 00:00:00
abstract：:Over the past few decades, understanding how tumor cells evade the immune system and their communication with their tumor microenvironment, has been the subject of intense investigation, with the aim of developing new cancer immunotherapies. The current therapies against cancer such as monoclonal antibodies against ch...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.07.012
更新日期：2020-05-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2012.02.009
更新日期：2012-08-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章
doi：10.1016/j.semcancer.2020.12.004
更新日期：2020-12-07 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2010.06.003
更新日期：2010-08-01 00:00:00
abstract：:The Signal Transducer and Activator of Transcription (STAT) family of proteins consists of transcription factors that play a complex and essential role in the regulation of physiologic cell processes, such as proliferation, differentiation, apoptosis and angiogenesis, and serves to organize the epigenetic landscape of...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.10.002
更新日期：2020-02-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
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更新日期：2020-02-01 00:00:00
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journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1994-02-01 00:00:00
abstract：:Cancer, being the most prevalent and resistant disease afflicting any gender, age or social status, is the ultimate challenge for the scientific community. The new generation therapeutics for cancer management has shifted the approach to personalized/precision medicine, making use of patient- and tumor-specific marker...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2019.08.023
更新日期：2019-08-20 00:00:00
abstract：:Utilization of thermal therapy (hyperthermia) is defined as the application of exogenous heat induction and represents a concept that is far from new as it goes back to ancient times when heat was used for treating various diseases, including malignancies. Such therapeutic strategy has gained even more popularity (ove...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2016.03.004
更新日期：2016-06-01 00:00:00
abstract：:Inhibition of Ras signalling has been a goal almost since its central role in cell signalling and its deregulation in disease were discovered. Early attempts at inhibiting its post-translational modification using peptidomimetics were successful in cell culture but failed spectacularly in clinical trials, making indus...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
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更新日期：2019-02-01 00:00:00
abstract：:While current treatment regimens for acute leukemia can dramatically improve patient survival, there remains room for improvement. Due to its roles in cell differentiation, cell survival, and apoptotic signaling, modulation of the cyclic AMP (cAMP) pathway has provided a meaningful target in hematological malignancies...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcancer.2020.02.004
更新日期：2020-02-07 00:00:00
abstract：:Angiogenesis, the growth of blood capillaries, is regulated by soluble growth factors and insoluble extracellular matrix (ECM) molecules. Soluble angiogenic mitogens act over large distances to initiate capillary growth whereas changes in ECM govern whether individual cells will grow, differentiate, or involute in res...
journal_title：Seminars in cancer biology
pub_type： 杂志文章,评审
doi：
更新日期：1992-04-01 00:00:00
