Abstract:
:The epidermal growth factor receptor (EGFR) has been widely used as a target for novel anticancer agents, such as blocking antibodies and small molecular weight tyrosine kinase compounds. In spite of recent advances in cancer cell biology, leading to the introduction of clinically active new drugs, such as cetuximab, panitumumab and erlotinib, unfortunately disease control remains unsuccessful due to the presence of constitutive resistance to EGFR inhibitors in most patients and the development of acquired resistance in the responders. A large number of molecular abnormalities in tumor cells seem to partly contribute to their resistance to anti-EGFR therapy: increased angiogenesis, constitutive activation of downstream mediators, overexpression of other tyrosine kinase receptors. Moreover, some mutations in the EGFR receptor kinase domain seem to play a crucial role in determining the sensitivity of cancer cells to specific inhibitors by altering the conformation of the receptor and its activity. The development of rational combinations of anticancer agents and EGFR inhibitors, able to exert synergistic cytotoxic interactions, has been widely accepted and used in both preclinical and clinical studies. Although the failure of large clinical trial based on empirical combination of anti-EGFR and classic chemotherapeutic agents, several preclinical data seems to support the hypothesis that combining EGFR inhibitors and other novel agents could efficiently inhibit tumor growth and overcome intrinsic resistance to a single-agent based therapy. This review focuses on the role of complementary signalling pathways in the development of resistance to EGFR targeting agents and the rationale to combine novel inhibitors as anticancer therapy.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Bianco R,Damiano V,Gelardi T,Daniele G,Ciardiello F,Tortora Gdoi
10.2174/138161207782360564subject
Has Abstractpub_date
2007-01-01 00:00:00pages
3358-67issue
33eissn
1381-6128issn
1873-4286journal_volume
13pub_type
杂志文章,评审abstract::Among pediatric patients, preterm neonates and newborns are the most vulnerable subpopulation. Rapid developmental changes of physiological factors affecting the pharmacokinetics of drug substances in newborns require extreme care in dose and dose regimen decisions. These decisions could be supported by in silico meth...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150901110533
更新日期:2015-01-01 00:00:00
abstract::Urological cancer refers to cancer in organs of the urinary system and the male reproductive system. It mainly includes prostate cancer, bladder cancer, renal cancer, etc., seriously threatening patients' survival. Although there are many advances in the treatment of urological cancer, approved targeted therapies ofte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200403131514
更新日期:2020-01-01 00:00:00
abstract::Ablation has become an important treatment for many pediatric patients with common supraventricular tachycardias (SVTs). Many multicenter studies have documented that radiofrequency (RF) catheter ablation is a safe and effective procedure for treatment of a large variety of SVTs in children and adults with a high succ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784007680
更新日期:2008-01-01 00:00:00
abstract::Metabolic syndrome (MetS) which is caused by poor dietary habits and sedentary behavior is a serious global health problem. MetS is a cluster of risk factors, represented by central obesity, hyperglycemia, dyslipidemia, and hypertension. In the 21st century, MetS and associated comorbidities, including obesity, diabet...
journal_title:Current pharmaceutical design
pub_type: 社论
doi:10.2174/138161282639201110165712
更新日期:2020-01-01 00:00:00
abstract::The activities of individual cells must be tightly coordinated in order to build and maintain complex 3- dimensional body structures during embryogenesis and regeneration. Thus, one way to view cancer is within systems biology as a network disorder affecting the ability of cells to properly interact with a morphodynam...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170530105837
更新日期:2017-01-01 00:00:00
abstract::Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts on motoneurons and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990341
更新日期:2013-01-01 00:00:00
abstract::There is extensive evidence that changes in immune system activation accompany the pathological changes of Alzheimer's disease (AD), but a mechanistic understanding of how the immune system actually participates in disease pathogenesis is still largely lacking. Because of the complexity of the immunological response, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774370843
更新日期:2005-01-01 00:00:00
abstract::The so-called demographic transition has changed the age structure of the population worldwide, with profound effects on societal organization. The growing number and percentage of old and very old people has compelled the scientific community to focus on age related diseases and peculiar consequences of aging itself ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777947533
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Neglected tropical diseases (NTDs) represent a serious problem in a number of countries around the world and especially in Africa and South America, affecting mostly the poor population which has limited access to the healthcare system. The drugs currently used for the treatment of NTDs are dated many decade...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201210115340
更新日期:2020-12-09 00:00:00
abstract::Psychoneuroimmunology is a relatively young field of research that investigates interactions between central nervous and immune system. The brain modulates the immune system by the endocrine and autonomic nervous system. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212802502305
更新日期:2012-01-01 00:00:00
abstract::Parkinson's disease (PD) is a movement disorder caused by degeneration of the nigrostriatal dopamine (DA) neurons in the substantia nigra pars compacta and the resultant deficiency in the neurotransmitter DA at the nerve terminals in the striatum. We and other investigators found increased levels of pro-inflammatory c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381620
更新日期:2005-01-01 00:00:00
abstract::RNA interference (RNAi) has quickly proven to be an immensely useful tool for studying gene function and validation of potential drug targets in almost all organisms that possess the required set of proteins of the interference pathway. In protozoan parasites like Plasmodium, Toxoplasma, Entamoeba, Giardia, Trypanosom...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990027
更新日期:2014-01-01 00:00:00
abstract::Both high arterial blood pressure (BP) and elevated levels of fine particulate matter (PM2.5) air pollution have been associated with an increased risk for several cardiovascular (CV) diseases, including stroke, heart failure, and myocardial infarction. Given that PM2.5 and high BP are each independently leading risk ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151109111712
更新日期:2016-01-01 00:00:00
abstract::Although somewhat controversial, there is good evidence that long-distance travel in general is a risk factor for venous thromboembolism, even in the absence of other risk factors. This is probably due to effects consequent to prolonged sitting but air travel in particular may be associated with risk factors other tha...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781662966
更新日期:2007-01-01 00:00:00
abstract::Obesity, a chronic low-grade inflammation disorder characterized by an expansion in adipose tissue mass, is rapidly expanding worldwide leading to an increase in the incidence of comorbidities such as insulin resistance, type 2 diabetes and cardiovascular diseases. This has led to a renewed interest in the adipose tis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151109111958
更新日期:2016-01-01 00:00:00
abstract::Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including cognition resulting i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803582522
更新日期:2012-01-01 00:00:00
abstract::DNA methyltransferase (DNMT) and histone deacetylase are key enzymes mediating the epigenetic regulation of gene expression. DNA hypermethylation and/or histone deacetylation in promoter regions is often associated with downregulation or silencing of transcription. Epigenetic silencing of tumor suppressor genes plays ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990527
更新日期:2014-01-01 00:00:00
abstract::Biodegradable particles have important applications in Drug Delivery Systems (DDS) of protein/peptide drugs. And recently, particle systems have also showed to be powerful for vaccine delivery (adjuvant) in order to solve the difficulties when conventional Alum adjuvant was used. However, in above applications, the pr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612821666150416100031
更新日期:2015-01-01 00:00:00
abstract::MicroRNA-34a (miR-34a) promotes apoptosis via down-regulating many anti-apoptotic proteins. Aldehyde dehydrogenase 2 (ALDH2) is an anti-apoptotic enzyme whose activity decline associates with myocardial injury. We tested hypothesis that miR-34a might play a pro-apoptotic role in myocardial infarction (MI) by down-regu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990325
更新日期:2013-01-01 00:00:00
abstract::Adenosine A(2A)-dopamine D(2) receptor interactions play a very important role in striatal function. A(2A)-D(2) receptor interactions provide an example of the capabilities of information processing by just two different G protein-coupled receptors. Thus, there is evidence for the coexistence of two reciprocal antagon...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784480108
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Fragile X syndrome (FXS) is the most common form of monogenic hereditary cognitive impairment, including intellectual disability, autism, hyperactivity, and epilepsy. METHODS:This article reviews the literature pertaining to the role of synaptic dysfunction in FXS. RESULTS:In FXS, synaptic dysfunction alte...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191102165206
更新日期:2019-01-01 00:00:00
abstract::Our clinical observations proved that the the duodenal ulcer in patients healed without any inhibition of gastric acid secretion (1965), and the healing rates of atropine vs cimetidine vs Carbenoxolone were equal and superior to that of placebo in randomized, prospective and multiclinical study of DU patients (1978). ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211796197016
更新日期:2011-01-01 00:00:00
abstract::In the early 1980s, an "atypical" beta-adrenergic receptor was discovered and subsequently called the beta (3)-adrenoceptor (beta(3)-AR). Agonists of the beta(3)-AR were observed to simultaneously increase lipolysis, fat oxidation, energy expenditure and insulin action leading to the belief that this receptor might se...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397339
更新日期:2001-09-01 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::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::Severe asthma is a complex heterogeneous disease with substantial unmet clinical need. Understanding the immunopathogenesis is likely to provide insights into potential novel therapies. To date researchers have focussed primarily at a single scale for example genome, cell or whole organ physiology. In this review we s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795429028
更新日期:2011-01-01 00:00:00
abstract::Understanding of the roles of RNAs within the cell has changed and expanded dramatically during the past few years. Based on fundamentally new insights it is now increasingly possible to employ RNAs as highly valuable tools in molecular biology and medicine. At present, the most important therapeutic strategies are ba...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210791792813
更新日期:2010-01-01 00:00:00
abstract::Reactive oxygen species (ROS), as well as reactive nitrogen species (RNS) play either harmful or beneficial role in biological systems. Beneficial effects of ROS include physiological roles in cellular responses against infectious agents and in several cellular signalling pathways. Harmful effects are due to high conc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789058084
更新日期:2009-01-01 00:00:00
abstract::The solid lipid nanoparticles (SLNs) usually consists of active drug molecules along with solid lipids, surfactants, and/or co-surfactants. They possess some potential features such as nano-size, surface with a free functional group to attach ligands, and as well they prove safe homing for both lipophilic as well as h...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190903155321
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Heat shock proteins are powerful endogenous cytoprotective proteins which help cells to survive recurrent cellular stress events. Identifying the underlying molecular mechanisms and molecular targets is especially interesting since it may help to develop new therapeutic strategies for the treatment of diseas...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160519113339
更新日期:2016-01-01 00:00:00