Abstract:
:Nuclear Hormone Receptors (NR) represent one of the most promising protein families in terms of therapeutic applications. These transcription factors are naturally switched on and off by small molecule hormones presenting physico-chemical properties very similar to therapeutic chemical entities. NRs represent therefore intrinsically a very good family of protein targets for the prevention and treatment of diverse diseases, including cancer. Several known anti-cancer drugs, such as tamoxifen or flutamide, are targeting NRs, and many more are expected to reach market. The detailed knowledge of the structural mechanism underlying activation and inhibition of NRs by small molecule modulators begets important therapeutic opportunities. The crystal structure of at least nine NR ligand binding domains (LBDs) revealed at the atomic level how natural or synthetic agonists and antagonists can promote recruitment of co-activator and co-repressor proteins. Interestingly, it was recently shown that nucleotide polymorphisms located in NR LBDs could alter or even reverse the response of the receptors to small molecule ligands. Mapping these polymorphisms on the structure of the LBD can reveal why agonists or antagonists become inactive against the mutated receptor, allow atomic models for resistance to cancer therapy, and open the door to the rational design of improved anti-cancer drugs, customized for each patient.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Schapira Mdoi
10.2174/1568009023333845keywords:
subject
Has Abstractpub_date
2002-09-01 00:00:00pages
243-56issue
3eissn
1568-0096issn
1873-5576journal_volume
2pub_type
杂志文章,评审abstract::The Jun oncoprotein is a major component of the transcription factor complex AP-1, which regulates the expression of multiple genes essential for cell proliferation, differentiation and apoptosis. Constitutive activation of endogenous AP-1 is required for tumor formation in avian and mammalian cell transformation syst...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009033333781
更新日期:2003-02-01 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
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abstract::Though modern available cancer therapies are effective, they possess major adverse effects, causing non-compliance to patients. Furthermore, the majority of the polymeric-based medication platforms are certainly not universally acceptable, due to their several restrictions. With this juxtaposition, lipid-based medicat...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009620666200115160805
更新日期:2020-01-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2012-06-01 00:00:00
abstract::Inactivation of the FHIT and TP53 genes is frequently observed in primary non-small cell lung cancers (NSCLC) and cell lines and may contribute to resistance to apoptotic stimuli elicited by various anti-tumor drugs. To evaluate a possible relationship between FHIT and TP53 status and response to platinum-analogue reg...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800908785133204
更新日期:2008-08-01 00:00:00
abstract::Following the discovery that defective retinoid signaling directly contributes to tumorigenesis, and, that retinoids have an anti-cancer effect in vitro and in vivo, retinoids have become part of the routine care in children with neuroblastoma at the stage of minimal residual disease. However, many patients still rela...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2011-09-01 00:00:00
abstract::Preferentially expressed antigen in melanoma (PRAME) is the best characterized member of the PRAME family of leucine-rich repeat (LRR) proteins. Mammalian genomes contain multiple members of the PRAME family whereas in other vertebrate genomes only one PRAME-like LRR protein was identified. PRAME is a cancer/testis an...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
abstract::Angiotensin II (Ang II), a main effector peptide of the renin-angiotensin system (RAS), mediates a hormonal action in the maintenance of blood pressure and electrolyte levels, and thus fluid homeostasis. Ang II also mediates paracrine, autocrine and/or intracrine actions in the control of various specific functions of...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911795538110
更新日期:2011-05-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2007-06-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2001-05-01 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::The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin-proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-a...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666151112122231
更新日期:2016-01-01 00:00:00
abstract::Gastrointestinal (GI) tumors are among the leading cause of death in cancer patients worldwide. Particularly, gastric cancer (GC) is the third cause of cancer deaths, whereas esophageal neoplasm is the eighth leading most common cancer worldwide and its incidence, especially adenocarcinoma type, is continuously increa...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170208162058
更新日期:2018-01-01 00:00:00
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::Glioma-associated oncogenes (GLIs) are zinc finger protein family members and downstream regulatory factors of the classic Hedgehog (Hh) signaling pathway. GLI proteins influence the growth and development of organisms and aid in tissue repair. However, aberrant expression of the GLI family member GLI1 promotes carcin...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2018-01-01 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::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::Haem oxygenase-1 (HO-1) catalyses the rate-limiting step in haem degradation. All three metabolites resulting from haem degradation (carbon monoxide (CO), biliverdin and free iron) have anti-inflammatory and anti-apoptotic properties. HO-1 is a stress-inducible enzyme found extensively expressed in a vast variety of b...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009614666140320111306
更新日期:2014-01-01 00:00:00
abstract::Head and neck cancer, the sixth most common type of cancer worldwide, is associated with a dismal prognosis that has minimally improved during the last few decades. Future advances in the treatment and prognosis of this fatal disease largely rely upon a better understanding of the molecular events that underlie tumor ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2004-12-01 00:00:00
abstract::Recent publications on the molecular characterization of malignant glioma have had profound impact on the appreciation of tumoral heterogeneity within and between patients. Both these phenomena are implicated in the variability in clinical outcome between patients, as well as the inevitable recurrence of these tumors ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160813191809
更新日期:2017-01-01 00:00:00
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journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113136660098
更新日期:2013-11-01 00:00:00
abstract::Cetuximab (IMC-C225, Erbitux ImClone Systems Inc, New York, NY) is a recombinant, human/mouse chimeric monoclonal antibody (MAb) that binds specifically to the extracellular domain of the human epidermal growth factor receptor (EGFR) on both normal and tumor cells, and competitively inhibits the binding of epidermal g...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
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更新日期:2010-02-01 00:00:00
abstract::Wild-type Wilms' tumor gene WT1 is expressed at high levels not only in most of acute myelocytic, acute lymphocytic, and chronic myelocytic leukemia, but also in various types of solid tumors including lung cancer. We tested the ability of the gene product (WT1) to serve as a target antigen for tumor specific immunot...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023334088
更新日期:2002-03-01 00:00:00
abstract::Tumor heterogeneity within various cancer types including breast carcinoma is pivotal in the manifestations of tumor hallmarks. Tumor heterogeneity is seen as a common landscape where intra-tumoral components including cellular and non-cellular factors create an interface with outside environment that leads to the uni...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009618666180628102247
更新日期:2019-01-01 00:00:00
abstract::Polyisoprenylated proteins (PPs) methylation by polyisoprenylated protein methyl transferase (PPMTase) is counteracted by polyisoprenylated methylated protein methyl esterase (PMPMEase). This is the only reversible step of the polyisoprenylation pathway as the relative amounts of the acid and ester forms are determine...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791859443
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:MicroRNA (miRNA) therapy, which was widely considered to treat a series of cancer, has been confronted with numerous obstacles to being delivered into target cells because of its easy biodegradation and instability. METHODS:In this research, we successfully constructed 11-mercaptoundecanoic acid modified go...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009618666181016144855
更新日期:2019-01-01 00:00:00
abstract::Actin was first identified in non-muscle cells only about three decades ago, and at about the same time, it was found that actin filaments were disrupted in the malignant transformed cells. The actin network is a rather complex, yet important structural and functional system of all eukaryotic cells. Actin filaments pr...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043332998
更新日期:2004-06-01 00:00:00
abstract::The integrin family of cell surface receptors integrates cell-extracellular matrix interactions with the cell cytoskeleton and signalling across the cell membrane, resulting in an important role in cell adhesion, mobility and migration, proliferation, and survival. Changes in the number and identity of integrin recept...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909788486713
更新日期:2009-06-01 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::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