Abstract:
:Our current understanding of cancer suggests that every tumour has individual features. Approaches to cancer treatment require thorough comprehension of the mechanisms triggering genomic instability and protecting cancer cells from therapeutic treatments. Base excision repair (BER) is a frontline DNA repair system that is responsible for maintaining genome integrity. The BER pathway prevents the occurrence of disease, including cancer, by constantly repairing DNA base lesions and DNA single strand breaks caused by endogenous and exogenous mutagens. BER is an important DNA repair system for cancer cell survival, as it can affect both chemoand radio-resistance of tumours. Variations in BER capacity are likely responsible for a number of cases of sporadic cancer and may also modulate cancer sensitivity and resistance to therapeutic treatments. For these reasons, it is broadly accepted that targeting BER enzymes might be a promising approach to personalised anti-cancer therapy. However, recent advances in both treatment strategies and the comprehension of cancer development call for a better understanding of the consequences of BER inhibition. Indeed, the impact on both the tumour microenvironment and healthy tissues is still unclear. This review will summarise the current status of the approaches exploiting BER targeting, describing the most promising small molecule inhibitors and synthetic lethality strategies, as well as potential limitations of these approaches.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Poletto M,Legrand AJ,Dianov GLdoi
10.2174/1381612823666170710123602subject
Has Abstractpub_date
2017-01-01 00:00:00pages
4758-4772issue
32eissn
1381-6128issn
1873-4286pii
CPD-EPUB-84640journal_volume
23pub_type
杂志文章,评审abstract:BACKGROUND:Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal disease, including heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large scale clinical trials of patients with or without diabet...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201103122813
更新日期:2020-11-03 00:00:00
abstract::Tumor necrosis factor alpha (TNF-α) is a multi-functional cytokine that regulates a variety of signaling pathways implicated in inflammation, immunity, cell death (apoptosis), cell survival (anti-apoptosis), and even tumorigenesis. TNF-α is predominantly produced by macrophages (or Kupffer cells within the liver), but...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990587
更新日期:2014-01-01 00:00:00
abstract::DNA methylation is an important regulatory component which influences phenotypes by modulating gene expression. Changes in DNA methylation may lead to altered phenotypes and ability of an organism to respond to stress leading to subsequent manifestation of life style diseases, cancer, etc. The human X chromosome repre...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990518
更新日期:2014-01-01 00:00:00
abstract::The nanodelivery of therapeutics into the brain will require a step-change in thinking; overcoming the blood brain barrier is one of the major challenges to any neural therapy. The promise of nanotechnology is that the selective delivery of therapeutics can be delivered through to the brain without causing secondary d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781368648
更新日期:2007-01-01 00:00:00
abstract::During the last two decades since the identification and characterization of T cell potassium channels great advances have been made in the understanding of the role of these channels in T cell functions, especially in antigen-induced activation. Their limited tissue distribution and the recent discovery that differen...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777585120
更新日期:2006-01-01 00:00:00
abstract::Stimulation of β-adrenergic receptors in the heart is the most effective endogenous way to increase the mechanical performance of cardiac tissues to meet the requirements of a fight-or-flight situation or stress. On the other hand, sustained activation of cardiac β-receptors initiates maladaptive remodeling of the myo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666141029111240
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:In spite of considerable efforts of researchers the cancer deseases remain to be incurable and a percentage of cancer deseases in the structure of mortality increases every year. At that, high systemic toxicity of antitumor drugs hampers their effective use. Because of this fact, the development of nanosyste...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190117095132
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Cancer and its treatment therapies, such as chemotherapy and radiotherapy, have negative effects on taste and smell functions. It is easy to explain smell and taste dysfunctions when a cancer involves the peripheric end organs or neurologic pathways of smell and taste. However, it is difficult to understand ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160216150956
更新日期:2016-01-01 00:00:00
abstract::Leptin has been shown to have a wide repertoire of peripheral effects, some of which are mediated through the central nervous system and others that are induced through a direct action on target tissues. There is now evidence showing that leptin exerts some of its metabolic effects acting directly on peripheral tissue...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033455369
更新日期:2003-01-01 00:00:00
abstract::Benzodiazepines (BZs) have been widely investigated in terms of clinical efficacy, factors underlying dependence, associated cognitive impairments, and interactions with psychotherapy for anxiety control. However, few studies have systematically considered manner of BZ administration in relation to these variables. St...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023396744
更新日期:2002-01-01 00:00:00
abstract::Food proteins contain latent biofunctional peptide sequences within their primary structures which may have the ability to exert a physiological response in vivo. A large range of biofunctional peptides have been isolated from food proteins including opioid, immunomodulatory, antimicrobial, mineral binding, growth and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780363068
更新日期:2007-01-01 00:00:00
abstract::Since the discovery of human immunodeficiency virus (HIV) as a causative agent of acquired immune deficiency syndrome (AIDS) various strategies were employed to counter its devastating actions. One such concept relies on the prevention of HIV entry into host's "competent" cells by means of compounds known as entry inh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319100003
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Human brain is amongst the most complex organs in human body, and delivery of therapeutic agents across the brain is a tedious task. Existence of blood brain barrier (BBB) protects the brain from invasion of undesirable substances; therefore it hinders the transport of various drugs used for the treatment of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200417141600
更新日期:2020-01-01 00:00:00
abstract::Free energy perturbation (FEP) theory coupled to molecular dynamics (MD) or Monte Carlo (MC) statistical mechanics offers a theoretically precise method for determining the free energy differences of related biological inhibitors. Traditionally requiring extensive computational resources and expertise, it is only rece...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799436421
更新日期:2012-01-01 00:00:00
abstract::An integrative synthesis of concepts and an explosion of experimental and epidemiological findings allow new insights as to how the interactions of genetic, environmental, dietary, cultural (social, psychological, economic) factors can influence the aging and diseases of aging processes. Although the net effect of the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786264106
更新日期:2008-01-01 00:00:00
abstract::Erectile dysfunction (ED) has multifactor pathogenesis, with neurological, vascular, endocrinological and psychogenic components described. However, about 50-85% of ED population report the presence of one or more comorbidities i.e. hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair endothel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778343046
更新日期:2006-01-01 00:00:00
abstract::Runx2/Cbfa/AML3 is a member of the runt homology domain family of transcription factors, essential for osteoblast differentiation and bone formation. Defining the molecular mechanisms by which Runx2 can function as a master regulatory gene for activating the program of osteoblastogenesis has provided novel insights fo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033453659
更新日期:2003-01-01 00:00:00
abstract::Development of effective drug delivery systems is important for medicine and healthcare. Polymer particulates (micro- and nanoparticles) have opened new opportunities in the field of drug delivery by overcoming various limitations of conventional delivery methods. The properties of polymeric particles can be readily t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160217125734
更新日期:2016-01-01 00:00:00
abstract::Sulphur mustard (SM; (2, 2'-dichloroethylsulfide)) was used for the first time in 1917, during the World War I. SM mainly induces DNA damage, oxidative stress, and inflammation. This compound injures the respiratory system, eyes, skin and the endocrine, gastrointestinal, and hematopoietic systems. However, due to the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180903112218
更新日期:2018-01-01 00:00:00
abstract::In the last two decades quantitative electroencephalogram (EEG) analysis has been widely used to investigate the neurophysiological characteristics of insomnia. These studies provided evidence in support of the hypothesis that primary insomnia is associated with hyperarousal of central nervous system and altered sleep...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786549326
更新日期:2008-01-01 00:00:00
abstract::Multidrug resistance (MDR) is a phenomenon through which tumor cells develop resistance against the cytotoxic effects of various structurally and mechanistically unrelated chemotherapeutic agents. The most consistent feature in MDR is overexpression and/or overactivity of ATP-dependent drug efflux transporters. Other ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151124234417
更新日期:2016-01-01 00:00:00
abstract::Coronary artery disease (CAD) ranks as the leading cause of death in the Western world. The most widely used therapeutics utilized for the treatment of CAD are the lipid-lowering drugs, which lower plasma cholesterol. However lowering cholesterol alone may not be sufficient to provide benefit to all patient population...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::The essential nature of rapid radiotracer synthesis very early in drug discovery programs has driven the need for better and more varied tritium incorporation methods. This review presents a summary of recent advances for tritium introduction via tritiated water, tritium gas, complex tritides, and a range of recently ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399969
更新日期:2000-07-01 00:00:00
abstract::Osteoblasts pass through a sequence of events controlled by hormones and transcriptional factors ensuring proper development of phenotype and functional properties until the osteoblast enter the osteocyte phenotype and/or undergo apoptosis. During its life cycle, the osteoblasts proliferate, deposit matrix proteins an...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013398167
更新日期:2001-03-01 00:00:00
abstract::Stability of a dosage form is its ability to preserve its quality attributes within preset limits. The time span over which these attributes remain within specifications is the shelf-life of the drug product. Stability is a very complex feature and is influenced not only by the stability of the drug substance but also...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160726094236
更新日期:2016-01-01 00:00:00
abstract::Synaptic transmission through descending motor pathways to lumbar motoneurons and then to leg muscles is essential for walking in humans and rats. Spinal cord injury (SCI), even when incomplete, results in diminished transmission to motoneurons and very limited recovery of motor function. Neurotrophins have emerged as...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990378
更新日期:2013-01-01 00:00:00
abstract::In the third millennium preventive medicine is becoming a corner stone in our concept of health. Colorectal cancer (CRC) fits the criteria of a disease suitable for prevention interventions. It is a prevalent disease that is associated with considerable mortality and morbidity rates, with more than 1,000,000 new cases...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781368783
更新日期:2007-01-01 00:00:00
abstract::Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent which is widely used for the induction and maintenance of anesthesia and for sedation in the intensive care unit. Propofol is an oil at room temperature and insoluble in aqueous solution. Present formulations consists of 1% or 2% (w/v) propofol, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043382846
更新日期:2004-01-01 00:00:00
abstract::G protein receptor kinase 2 (GRK2) has been for years mainly considered the negative regulator of the cardiac β adrenergic signaling. However GRK2 is a ubiquitous molecule and its kinase activity and scaffold properties brought to several investigations which have evidenced its involvement in pathophysiology of extra-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799040493
更新日期:2012-01-01 00:00:00
abstract::Fibrate derivatives have a 40-year history in the management of dyslipidemia. Although this class of drugs is generally well tolerated, several safety issues have arisen from their use. In the present article we review the literature describing side effects associated with the use of fibrates except for those that are...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208783885362
更新日期:2008-01-01 00:00:00