Abstract:
:Cell proliferation, differentiation, and survival are regulated by a number of extracellular hormones, growth factors, and cytokines in complex organisms. The transduction of the signals by these factors from the outside to the nucleus often requires the presence of small intracellular proteins (i.e. ras and other small G proteins) that are linked to the plasma membrane through a isoprenyl residue that functions as hydrophobic anchor. Isoprenylation is a complex process regulated by different enzymatic steps that could represent potential molecular targets for anti-cancer strategies. In the present paper the different transduction pathways regulated by some isoprenylated proteins such as ras and other small G proteins are described. Moreover, the molecular mechanisms of the isoprenylation process and the mode of action of the different isoprenylation inhibitors are discussed with attention to statins, farnesyltransferase inhibitors (FTI) and aminobisphosphonates. The role of different candidate targets in the determination of anti-tumour effects by FTIs is also described in order to define potential molecular markers predictor of clinical response. On the basis of several preclinical data, new strategies based on multi-step enzyme inhibition or on target prioritization are proposed in order to enhance the anti-tumour activity of agents inhibiting isoprenylation. Finally, a summary of the principal data on clinical trials based on the use of FTIs and statins is given. In conclusion, the inhibition of isoprenylation is an attractive, but still not completely investigated therapeutic alternative that requires optimization for the translation in the current treatment of neoplasms.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Caraglia M,Budillon A,Tagliaferri P,Marra M,Abbruzzese A,Caponigro Fdoi
10.2174/1389450053765833keywords:
subject
Has Abstractpub_date
2005-05-01 00:00:00pages
301-23issue
3eissn
1389-4501issn
1873-5592journal_volume
6pub_type
杂志文章,评审abstract::Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions (i.e. >2 log tumor ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011794815301
更新日期:2011-03-01 00:00:00
abstract::Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heav...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150506114336
更新日期:2016-01-01 00:00:00
abstract::Efforts to interfere with the initiation and promotion of breast and other cancers by endocrine manipulation are not new. It is of obvious benefit to cancer patients to administer substances that combine minimal general toxicity with maximal oestrogen inhibition. Raloxifene is a relatively recent addition to a group o...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450013348263
更新日期:2001-12-01 00:00:00
abstract::RNA, as an intermediate in the production of every gene encoded protein and the genetic material of many pathogenic viruses, presents an attractive target for both biological and therapeutic manipulation. Despite its extensive involvement in living systems, its chemical diversity based on four units is relatively low ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450023347722
更新日期:2002-06-01 00:00:00
abstract::Over the past years, there was an explosion in the knowledge of the protein target and molecular mechanism associated with various disease types and in the new research of drugs of natural origin. The key idea is to evaluate bioactive natural products interacting with protein domains of different genetic origin but st...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011794815284
更新日期:2011-03-01 00:00:00
abstract::The prevalence of periodontitis is around 20-50% of global population. If not treated, it can cause of tooth loss. Periodontal treatment aims at preserving the patient's teeth from various methods, including infection control and restoring lost periodontal tissue. The periodontium has great biological regenerative pot...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121999201105152639
更新日期:2020-11-05 00:00:00
abstract::Using a portable infusion pump, intravenous opioid patient-controlled analgesia (PCA) permits a patient to self-deliver a small bolus of opioid to achieve prompt relief without over sedation. Use of PCA for pain management is increasing in hospitals, largely because it can provide equivalent or better analgesia than c...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945005774574524
更新日期:2005-11-01 00:00:00
abstract::Diacylglycerol (DAG) kinase (DGK) modulates the balance between the two signaling lipids, DAG and phosphatidic acid (PA), by phosphorylating (consuming) DAG to yield PA. Ten mammalian DGK isozymes have been identified to date. In addition to two or three cysteine-rich C1 domains (protein kinase C-like zinc finger stru...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008785132394
更新日期:2008-08-01 00:00:00
abstract::The overuse of antibiotics which exerts the selective pressure for bacterial pathogens has facilitated the spread of antibiotics' resistance. Metallo-β-lactamases (MβLs) are zinc enzymes produced by an increasing number of bacterial pathogens. They can readily cleave carbapenems and most other β-lactams that are mains...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140326094504
更新日期:2014-01-01 00:00:00
abstract::NMDA receptors are a subclass of excitatory, ionotropic L-glutamate neurotransmitter receptors. They are.heteromeric, integral membrane proteins being formed by the assembly of the obligatory NR1 subunit together with modulatory NR2 subunits of which four different types, NR2A-NR2D, have been described. This results i...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450013348461
更新日期:2001-09-01 00:00:00
abstract::Patients with heart failure undergoing non-cardiac surgery still have an unacceptably high morbidity and mortality. Compromised myocardial physiologic reserves in combination with extensive surgery and anesthesia appear to play a crucial role in determining high perioperative morbidity and mortality. Nevertheless, sev...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/138945009789108819
更新日期:2009-09-01 00:00:00
abstract::Multidrug resistance (MDR) is a kind of acquired resistance of microorganisms and cancer cells to chemotherapic drugs that are characterized by different chemical structure and different mechanism of action. Classic MDR is the consequence of the over-expression of a variety of proteins that extrude the chemotherapic f...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006777709520
更新日期:2006-07-01 00:00:00
abstract::Virtual screening for active compounds has become an essential step within the drug development pipeline. The computer based prediction of compound binding modes is one of the most time and cost efficient methods for screening ligand libraries and enrich results of potential drugs. Here we present an overview about cu...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160201105806
更新日期:2016-01-01 00:00:00
abstract::The present article aims to review the literature on the relationship between psychology and inflammatory bowel disease (IBD). In particular, the first section is dedicated to explore the role of psychological factors in the etiopathology of the disease, its development and the efficacy of treatments, while the second...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140627151702
更新日期:2014-01-01 00:00:00
abstract::Antimicrobial resistance of human pathogenic bacteria is an emerging problem for global public health. This resistance is often associated with the overproduction of membrane transport proteins that are capable to pump chemotherapeutics, antibiotics, detergents, dyes and organic solvents out of the cell. In Gram-negat...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008785747789
更新日期:2008-09-01 00:00:00
abstract::Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation affecting the colonic mucosa, that can extend to the whole large bowel. The severity of mucosal lesions directly reflects the disease activity and severity and may be prognostic for an aggressive behavior of the pathol...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011796818216
更新日期:2011-09-01 00:00:00
abstract::Due to potential health benefits and the general assumption that natural products are safe, there is an increasing trend in the general population - including pregnant women - to supplement their diet with flavonoid-based food supplements. In addition, preclinical studies aim to prevent developmental adverse effects i...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150804110049
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1573399811666150615145409
更新日期:2018-01-01 00:00:00
abstract::Hepatitis C virus (HCV), a member of the Flaviviridae family, has been recognised to be responsible for both parenterally transmitted and sporadic non-A and non-B hepatitis affecting 1-3% of the world population. HCV is a positive stranded RNA virus encoding a single polyprotein which contains at least ten unique stru...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450023347650
更新日期:2002-08-01 00:00:00
abstract::Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threating conditions still lacking a definite therapy and carrying a high mortality and morbidity, especially in children and infants. Albeit respiratory assistance and supportive therapies are crucial for ALI/ARDS, many drugs have been pr...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012800675687
更新日期:2012-06-01 00:00:00
abstract::Hepatic diseases are turning into one of the few diseases that cannot be effectively cured due to some reasons although various receptors existed in the liver. Currently, several passive targeting delivery systems have been used in the drug/gene delivery for the treatment of hepatic diseases. For example, Zinostatin s...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140309232100
更新日期:2014-06-01 00:00:00
abstract:BACKGROUND:It becomes increasingly evident that the SARS-CoV-2 infection is not limited to the respiratory system. In addition to being a target of the virus, the kidney also seems to have a substantial influence on the outcomes of the disease. METHODS:Data was obtained by a comprehensive and non-systematic search in ...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121999201013151300
更新日期:2021-01-01 00:00:00
abstract::The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play an important role in the generation of pacemaker activity of cardiac sinoatrial node cells and immature cardiomyocytes. HCN channels are also present in adult atrial and ventricular cardiomyocytes, where the physiological role is currently und...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150531152047
更新日期:2015-01-01 00:00:00
abstract::Currently, low density lipoprotein cholesterol (LDL-C) levels are the main, if not the only, lipid target in the effort to reduce cardiovascular disease (CVD) morbidity and mortality. Several primary and secondary CVD prevention trials with statins shaped current guidelines and provided detailed targets across a range...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007780058933
更新日期:2007-03-01 00:00:00
abstract::Diabetes is reaching epidemic proportions worldwide. Many dietary compounds have been found to exert health beneficial effects against different pathologies including diabetes. Most bioactive compounds have been identified in fruits and vegetables and their mechanisms of action explored both in vitro and in vivo. In p...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666151001105230
更新日期:2017-01-01 00:00:00
abstract::HIV-1 replicates by infecting new target cells either as cell-free viral particle or, much more efficiently, via cell-to-cell viral transmission. Cell-mediated viral spread, in which the infected cell directly transfers the viral particles to target cells via cell-cell contacts, in vitro is up to three orders of magni...
journal_title:Current drug targets
pub_type: 杂志文章
doi:
更新日期:2015-08-25 00:00:00
abstract::Androgen and androgen receptor (AR) play a critical role in the development of prostate cancer. Androgen deprivation therapy (ADT) has become the therapeutic mainstay for patients with metastatic prostate cancer. ADT can reduce the serum testosterone level from the normal range between 500 and 600 ng/dl to the castrat...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666141024114736
更新日期:2014-01-01 00:00:00
abstract::Enzymes are proteins that act as biological catalysts to speed up cellular biochemical processes. According to their main Enzyme Commission (EC) numbers, enzymes are divided into six categories: EC-1: oxidoreductase; EC-2: transferase; EC-3: hydrolase; EC-4: lyase; EC-5: isomerase and EC-6: synthetase. Different enzym...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666181002143355
更新日期:2019-01-01 00:00:00
abstract::Withdrawn by the publisher. ...
journal_title:Current drug targets
pub_type: 杂志文章
doi:
更新日期:2015-02-12 00:00:00
abstract::A group of oxytocinergic neurons originating in the paraventricular nucleus of the hypothalamus and projecting to extrahypothalamic brain areas (e.g. hippocampus, medulla oblongata and spinal cord) control penile erection. Activation of these neurons by dopamine and dopamine agonists, excitatory amino acids (N-methyl-...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450033347190
更新日期:2003-01-01 00:00:00