Abstract:
:The histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell cycle arrest, differentiation and/or apoptosis. Histone acetylation and deacetylation play important roles in the modulation of chromatin topology and the regulation of gene transcription. Histone deacetylase inhibition induces the accumulation of hyperacetyl-ated nucleosome core histones in most regions of chromatin but affects the expression of only a small subset of genes, leading to transcriptional activation of some genes, but repression of an equal or larger number of other genes. Non-histone proteins such as transcription factors are also targets for acetylation with varying functional effects. Ace-tylation enhances the activity of some transcription factors such as the tumor suppressor p53 and the erythroid differentiation factor GATA-1 but may repress transcriptional activity of others including T cell factor and the co-activator ACTR. Recent studies in our laboratory and others have shown that the estrogen receptor alpha (ERalpha) can be hyperacetylated in response to histone deacetylase inhibition, suppressing ligand sensitivity and regulating transcriptional activation by histone deacetylase inhibitors. Conservation of the acetylated ERalpha motif in other nuclear receptors suggests that acetylation may play an important regulatory role in diverse nuclear receptor signaling functions. A number of structurally diverse histone deacetylase inhibitors have shown potent antitumor efficacy with little toxicity in vivo in animal models. Several compounds are currently in early phase clinical development as potential treatments for solid and hematological cancers both as monotherapy and in combination with cytotoxics and differentiation agents. This report reviews the biology and clinical development of histone deacetylase inhibitors for cancer therapy.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Vigushin DM,Coombes RCdoi
10.2174/1568009043481560keywords:
subject
Has Abstractpub_date
2004-03-01 00:00:00pages
205-18issue
2eissn
1568-0096issn
1873-5576journal_volume
4pub_type
杂志文章,评审abstract::Coordination between the amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme β-klotho has been found to play pivotal roles in mediating tumor development and progression. Aberrant FGF19-FGFR4 signaling has b...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009618666180319091731
更新日期:2019-01-01 00:00:00
abstract::UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in O-glycosylation of proteins. Glycosylated proteins play important role...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160922102641
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and prom...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009617666170427110450
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Intestinal β-glucuronidase enzyme has a significant importance in colorectal carcinogenesis. Specific inhibition of the enzyme helps prevent immune reactivation of the glucuronide- carcinogens, thus protecting the intestine from ROS (Reactive Oxidative Species) mediatedcarcinogenesis. OBJECTIVES:Advancement...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009619666190320102238
更新日期:2019-01-01 00:00:00
abstract::Scaffold-based analogs of cinnamic acid benzyl amide (CABA) exhibit pleiotropic effects in cancer cells, and their exact molecular mechanism of action is under investigation. The present study is part of our systemic analysis of interactions of CABA analogs with their molecular targets. These compounds were shown to i...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009614666140821122718
更新日期:2014-01-01 00:00:00
abstract::Amplification of the HER-2 gene occurs in approximately 25% of breast cancers, causing up-regulation of key signaling pathways which control cell growth and survival. In breast cancer patients, HER-2 overexpression correlates with an aggressive phenotype and poor prognosis. HER-2, therefore, has become the focus of ma...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909788166484
更新日期:2009-05-01 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is a key protein kinase controlling signal transduction from various growth factors and upstream proteins to the level of mRNA translation and ribosome biogenesis, with pivotal regulatory effects on cell cycle progression, cellular proliferation and growth, autophagy and angiogenes...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791517172
更新日期:2010-08-01 00:00:00
abstract::(5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of the Cp2TiCl2 catalyst giving 2,5-dialkylydenemagnesacyclopentane in 86% yield. The acid hyd...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009615666150506093155
更新日期:2015-01-01 00:00:00
abstract::Copper is a trace element which is tightly regulated in mammals and lower animals. Disruptions of copper homeostasis in humans are rare and they cause serious disorders such as Wilson's disease and Menke's disease. Copper plays an important role in promoting physiological and malignant angiogenesis. Formation of new b...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800905774574066
更新日期:2005-11-01 00:00:00
abstract::Targets for cancer therapy are conventionally selected by identification of molecules acting downstream of established tumour suppressors and oncoproteins, such as p53, c-Myc and Ras. However, the forward genetics approach provides an alternative, conceptually distinct, strategy for identifying target molecules de nov...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract::Obesity is rapidly becoming a global phenomenon. This is more than a cosmetic issue as obesity is associated with several life-threatening diseases, including colon cancer. Insulin resistance and inflammation, underlying factors in obesity-related diseases, promote colonocyte proliferation and suppress programmed cell...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908786241087
更新日期:2008-11-01 00:00:00
abstract::Prevention is one of the most important and promising strategies to control cancer. Many dietary bioactive compounds, mostly phytochemicals, have been found to decrease the risk of carcinogenesis. Modulating the metabolism and disposition pathways of carcinogens represents one of the major mechanisms by which dietary ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781386669
更新日期:2007-08-01 00:00:00
abstract::Although the imatinib based therapy of chronic myeloid leukemia (CML) represents a triumph of medicine, not all patients with CML benefit from this drug due to the development of resistance and intolerance. The interruption of imatinib treatment is often followed by clinical relapse, suggesting a failure in the killin...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113139990083
更新日期:2013-09-01 00:00:00
abstract::Gardenia, the fruit of Gardenia jasminoides Ellis, has been widely used to treat liver and gall bladder disorders in Chinese medicine. It has been shown recently that geniposide, the main ingredient of Gardenia Fructus, exhibits the anti-tumor effect. In this review, we discuss the anti-tumor effect and possible mecha...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009054064633
更新日期:2005-06-01 00:00:00
abstract::The urokinase plasminogen activator (uPA) system (uPAS) consists of the uPA, its cognate receptor (uPAR) and two specific inhibitors, the plasminogen activator inhibitor 1 (PAI-1) and 2 (PAI-2). The uPA converts the proenzyme plasminogen in the serine protease plasmin, involved in a number of physiopathological proces...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909787314002
更新日期:2009-02-01 00:00:00
abstract::Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attrac...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800910793357907
更新日期:2010-12-01 00:00:00
abstract::Various signal transduction pathways have been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL), which is characterized by the progressive accumulation of monoclonal CD5+ B cells in the blood. B cell receptor (BCR) signaling appears to have a crucial role in disease onset and is thought to be induc...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160408145623
更新日期:2016-01-01 00:00:00
abstract::Lipophilic derivatives of the anticancer drug paclitaxel (PTX) were prepared by means of its conjugation to lipoamino acid (LAA) residues, with the aim of increasing drug accumulation in tumor cells. PTX was linked to the methyl esters of norleucine (C6) or 2-aminodecanoic acid (C10). A succinic acid group was used as...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800909787580944
更新日期:2009-03-01 00:00:00
abstract::Human mesenchymal stem cells (hMSCs) consist of cells that can differentiate into mesenchymal tissues, including osteoblasts, adipocytes and chondrocytes. hMSCs constitute a particular stem cell niche in the stromal compartment of the bone marrow, and also play a role in maintaining the normal function of haematopoiet...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791208553
更新日期:2010-06-01 00:00:00
abstract::Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800911795656001
更新日期:2011-06-01 00:00:00
abstract::Aberrant expression of the RON receptor tyrosine kinase contributes to breast cancer malignancy. Although clinical trials of RON targeting are underway, the intriguing issue is the diversity of RON expression as evident by cancer cells expressing different variants including oncogenic RON160. The current study determi...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/15680096113139990038
更新日期:2013-07-01 00:00:00
abstract::Therapeutic vaccines continue to be one of the most active fields in cancer research. However, despite clear evidence of antitumor effect in laboratory animals, and despite the ability of current vaccine candidates to elicit tumor specific antibodies and T-cells in humans, objective responses in the clinical trials ar...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911793743583
更新日期:2011-01-01 00:00:00
abstract::FOXO proteins are evolutionarily conserved transcription factors implicated in several fundamental cellular processes, functioning as end-point for transcriptional programs involved in apoptosis, stress response and longevity. Abrogation of FOXO function is very frequent in human cancer, therefore the mechanisms of re...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800910791054158
更新日期:2010-03-01 00:00:00
abstract::Angiogenesis is crucial for tumor development and progression, and antiangiogenetic therapy represents a promising approach for cancer treatment. Thus, the in-depth understanding of the molecular mechanism(s) regulating angiogenesis, together with the characterization of molecules expressed by endothelial cells and in...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009033481741
更新日期:2003-12-01 00:00:00
abstract::Several subtypes of T cells are located in a tumor environment, each of which supplies their energy using different metabolic mechanisms. Since the cancer cells require high levels of glucose, the conditions of food poverty in the tumor environment can cause inactivation of immune cells, especially the T-effector cell...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200720010647
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Osteosarcoma is an aggressive bone tumor. Itrepresents the principal cause of cancer-associated death in children.Considering the recent findings on the role of iron in cancer, iron chelation has been investigated for its antineoplastic properties in many tumors. Deferasirox is the most used iron chelator co...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666201230090531
更新日期:2020-12-29 00:00:00
abstract::Drug delivery systems are under intense investigation all around the world, especially in oncology research. Indeed, in some cases, like bone metastasis, nanodrugs may represent the last and best choice for both treatment and imaging of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as radi...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009615666150407125020
更新日期:2015-01-01 00:00:00
abstract::NUPR1 is a transcription factor that has attracted great attention because of its various roles in cancer. Several studies were carried out to determine its molecular targets and mechanism of action to develop novel therapies against cancer. Here, we shed light on the role of NUPR1 in different types of cancer. NUPR1 ...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200703152523
更新日期:2020-01-01 00:00:00
abstract::AKT is a central signaling molecule in regulating cell survival, proliferation, tumor growth and angiogenesis. Upstream components of AKT signaling pathway such as PI3K, PTEN, and Ras are commonly mutated in many human cancers. Recently it is found that AKT plays an important role in regulating normal vascularization ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908783497122
更新日期:2008-02-01 00:00:00
abstract::With increasing incidence of cancer at most of the sites, and growing economic burden and associated psychological and emotional trauma, it is becoming clearer that more efforts are needed for cancer cure. Since most of the chemotherapeutic drugs are non-selective because they are also toxic to the normal cells, new a...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907780809732
更新日期:2007-06-01 00:00:00