Abstract:
:The outcome of patients with gastrointestinal stromal tumors has been dramatically improved by therapy with imatinib mesilate (imatinib mesylate), a KIT and platelet-derived growth factor (PDGFR) tyrosine kinase inhibitor. Unfortunately, the majority of patients eventually experience disease progression due to drug resistance. Recent elucidation of the mechanisms of resistance to imatinib, particularly the acquisition of secondary mutations of the KIT and PDGF receptors, has provided significant insight and potential for the development of novel therapies. This review discusses the efficacy of sunitinib, which is approved for the treatment of patients with imatinib-resistant tumors, and highlights a number of emerging second-generation receptor tyrosine kinase inhibitors that show therapeutic potential in imatinib-resistant patients. Also considered are several promising agents targeting pathways downstream of the constitutionally activated KIT and PDGF receptors. Strategies to overcome imatinib resistance by optimizing combination therapy and selecting specific kinase inhibitors based on the secondary mutations identified in tumors of individual patients are presented.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Sankhala KK,Papadopoulos KPdoi
10.1517/13543784.16.10.1549subject
Has Abstractpub_date
2007-10-01 00:00:00pages
1549-60issue
10eissn
1354-3784issn
1744-7658journal_volume
16pub_type
杂志文章,评审abstract::Presentations at the William Harvey Research Conference on PDE Inhibitors described the molecular biology, biochemical regulation. pharmacology, and therapeutic utility of inhibitors of cyclic nucleotide phosphodiesterases (PDEs). Most of the talks focused on PDE4 and PDE5. two members of the 11-member PDE family that...
journal_title:Expert opinion on investigational drugs
pub_type:
doi:10.1517/13543784.9.3.621
更新日期:2000-03-01 00:00:00
abstract::The discovery of new antibacterial drugs can be based either upon empirical screening methods or structure-based design. Empirical methods utilise both intact bacteria and isolated biochemical targets for high throughput screening of natural product or chemical libraries to detect inhibitor leads. Structure-based meth...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.8.1019
更新日期:1997-08-01 00:00:00
abstract:INTRODUCTION:IL-6 is a key cytokine in the pathogenesis of rheumatoid arthritis (RA). The clinical efficacy of tocilizumab (TCZ), a humanized anti-IL6-receptor mAb, confirmed the value of IL-6 blockade in this disease. A number of new anti-IL-6 biologics are currently in Phase I - III of clinical development for RA. A...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.912276
更新日期:2014-07-01 00:00:00
abstract::'Male factor' problems contribute to subfertility in a significant proportion of couples. In some instances, defective sperm production has qualitative and/or quantitative effects on the semen profile; in others, no obvious defects can be detected, yet spermatozoa are non-fertilising. Recent studies have revealed that...
journal_title:Expert opinion on investigational drugs
pub_type: 社论
doi:10.1517/13543784.6.12.1797
更新日期:1997-12-01 00:00:00
abstract::Asthma is a serious world health problem characterised by a chronic inflammatory disorder of the airways. Asthma attacks, or exacerbations, are episodic but airway inflammation is chronically present. Thus, this disorder requires long-term management. The goals of asthma management include prevention steps for long-te...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.1.49
更新日期:2002-01-01 00:00:00
abstract::Control of the immune system is of indispensable importance for graft acceptance and function. Immunological changes in the graft before and after organ harvesting, the transplantation procedure itself and the organ recipients clinical state contribute to the immune response. Leukocyte trafficking [1] into a graft is ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.4.789
更新日期:2000-04-01 00:00:00
abstract::Liver targeted therapy is designed to deliver a substance preferentially to the organ in order to increase the accumulation, improve the therapeutic effect and reduce toxicity to other organs. The aim of selective targeting is to deliver a substance to a specific cell type in the liver. A variety of vehicles have been...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.11.1795
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND:Malaria continues to exact a huge toll on the health of residents of endemic countries. Thus, new approaches to prevention and treatment are needed. OBJECTIVE:To provide an update on novel therapies for the prevention of malaria. METHODS:Systematic MEDLINE search from 1956 to 2008 using the search term 'ma...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780802514039
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Interferon-alpha (IFN-α) is the traditional therapeutic agent for chronic myeloid leukemia (CML). The molecular mechanism of IFN-α efficacy in the treatment of CML is not fully clear. OBJECTIVES:To identify the peptides and/or proteins that bind to the proteins specifically expressed on the surface of IFN-α...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.2011.632407
更新日期:2011-12-01 00:00:00
abstract:INTRODUCTION:In asthma, most commonly, 'conventional' anti-inflammatory medications represented by inhaled corticosteroids and leukotriene inhibitors are effective. In some patients however additional inhibition of the airways inflammation is necessary. Such compounds might be molecules inhibiting specifically certain ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1227319
更新日期:2016-10-01 00:00:00
abstract:INTRODUCTION:Crizotinib is a first-in-class ALK tyrosine kinase inhibitor (TKI), which has proven its superiority over standard platinum-based chemotherapy for the first-line therapy of ALK-rearranged non-small cell lung cancer (NSCLC) patients. The development of acquired resistance to crizotinib represents an ongoing...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1324572
更新日期:2017-06-01 00:00:00
abstract:INTRODUCTION:The fast actions of the excitatory neurotransmitter glutamate are mediated by glutamate-gated ion channels (ionotropic Glu receptors). Metabotropic glutamate receptors (mGlus) are coupled to second messenger pathways via G proteins and modulate glutamatergic and GABAergic neurotransmission. Of the eight di...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.986264
更新日期:2015-04-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Migraine is an episodic, substantially inherited brain disorder affecting 15% of adults in Western Europe and North America, and is one of the commonest reasons for patients to see their physicians. While the World Health Organization considers that severe migraine can be as disabling as quadrip...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543781003691832
更新日期:2010-04-01 00:00:00
abstract::While oral formulations of agonists at the serotonin (5-HT) receptor subdivisions 5-HT(1B/1D)--the "triptan" class of drugs--dominate the market for migraine therapy and while still more triptans are under development, recent research efforts have also explored other pharmacological avenues, which are mostly based on ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.12.1813
更新日期:2002-12-01 00:00:00
abstract:INTRODUCTION:Heat shock protein 90 (HSP90) serves as a critical facilitator for oncogene addiction. There has been augmenting enthusiasm in pursuing HSP90 as an anticancer strategy. In fact, since the initial serendipitous discovery that geldanamycin (GM) inhibits HSP90, the field has rapidly moved from proof-of-concep...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.902442
更新日期:2014-05-01 00:00:00
abstract::Therapeutic angiogenesis has yielded promising results in animal models, including the demonstration of newly created blood vessels, increased perfusion and functional benefits. On the other hand, clinical studies using similar methods of angiogenesis have so far been disappointing. The possibility that endothelial dy...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.1.37
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Oxidative stress toxicity (OST) has been implicated in almost all pathological conditions. Despite the widespread use of natural antioxidants, no pharmaceutical antioxidants have yet been developed or prescribed in medical practise. Antioxidant drugs such as Deferiprone and N-acetylcysteine can target esse...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1631284
更新日期:2019-07-01 00:00:00
abstract:INTRODUCTION:Despite the substantial reduction in cardiovascular morbidity and mortality after the management of dyslipidemia with statins, residual risk remains even after achieving low-density lipoprotein cholesterol targets. This residual risk appears to be partly attributed to low levels of high-density lipoprotein...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1582028
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Histone deacetylases (HDACs), which target histones as well as non-histone proteins as substrates, have the potential to regulate aberrant gene expression and restore normal growth control in malignancies. OBJECTIVE:This review provides an updated summary of preclinical and clinical experience with the oral...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.8.1247
更新日期:2008-08-01 00:00:00
abstract:INTRODUCTION:Due to improvements in our understanding of the pathogenesis of systemic lupus erythematosus (SLE), several target drugs have been and are being developed. One of the possible targets in SLE is co-stimulation between antigen-presenting cells and T cells. Abatacept is a co-stimulation moderator approved for...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2016.1154943
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Chronic hepatitis C virus (HCV) infection is a worldwide health problem. Response rates to current standard of treatment (pegylated IFNs and ribavirin) are low in patients with the prevailing genotype 1. OBJECTIVE:To review papers published or presented at recent international meetings showing the results o...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.11.1635
更新日期:2008-11-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The sodium/hydrogen exchanger-1 (NHE-1/SLC9A1) is a ubiquitous plasma membrane protein whose main role is maintenance of intracellular pH and volume. NHE-1 plays a role in atherogenesis; however, its clinical relevance has not yet been established. AREAS COVERED IN THIS REVIEW:We herein review ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.532123
更新日期:2010-12-01 00:00:00
abstract::The eating disorders anorexia nervosa, bulimia nervosa and binge eating disorder are common, significant public health problems which are treated with nutritional, psychotherapeutic and pharmacological interventions. A number of drugs (mostly antidepressant drugs) are currently used in their treatment to some benefit,...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.3.491
更新日期:2003-03-01 00:00:00
abstract::The beneficial effect of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of eviden...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.10.1847
更新日期:2001-10-01 00:00:00
abstract::Bromocriptine, a potent dopamine D(2) receptor agonist, has been shown to reduce insulin resistance, glucose intolerance and hyperlipidaemia in both numerous animal studies and in Phase II studies. Bromocriptine has been used worldwide for over 20 years to treat Parkinson's disease, macroprolactinoma and other disorde...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.10.1683
更新日期:1999-10-01 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative disorder associated with the loss of dopaminergic neurons in the substantia nigra. The decline of dopamine leads to motor dysfunctions manifested as tremor, rigidity and bradykinesia. The pharmacological treatment of choice for the past 30 years has primarily been the do...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.8.1335
更新日期:2003-08-01 00:00:00
abstract::Major depressive disorder (MDD) is a serious illness with far reaching societal and economic ramifications. The monoamine-deficiency hypothesis that depressive symptoms are associated with reductions in monoamine neurotransmission, particularly serotonin and noradrenaline, is supported by both neurochemical findings a...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.4.531
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND:With 170 million people infected worldwide and an inadequate current standard of care, hepatitis C virus (HCV) infection represents a major unmet medical need. Multiple companies are working on the discovery and development of specific HCV antiviral drugs, including inhibitors of HCV polymerase, protease and...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.3.303
更新日期:2008-03-01 00:00:00
abstract::Phytoestrogens, such as the soya isoflavones genistein and daidzein, are currently being extensively investigated through both molecular, preclinical and clinical studies to determine their potential health benefits. Phytoestrogens may protect against chronic diseases such as hormone-dependent cancer (e.g., breast and...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.8.1829
更新日期:2000-08-01 00:00:00
abstract::Asthma and chronic obstructive pulmonary disease (COPD) are diseases of the airways with an underlying inflammatory component. The prevalence and healthcare burden of asthma and COPD is still rising and is predicted to continue to rise in the current century. The beta-agonists and corticosteroids form the basis of the...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.1.5
更新日期:2003-01-01 00:00:00