Abstract:
INTRODUCTION:The highly divergent histological heterogeneities, aggressive invasion and extremely poor response to treatment make glioblastoma (GBM) one of the most lethal and difficult cancers in humans. Among key elements driving its behavior is epidermal growth factor receptor (EGFR), however, neither traditional therapy including neurosurgery, radiation, temozolomide, nor targeted EGFR therapeutics in clinic has generated promising results to date. Strategies are now focusing on blocking the downstream EGFR-activated metabolic pathways and the key phosphorylated kinases. AREAS COVERED:Here, we review two major EGFR-activated downstream metabolic pathways including the PI3K/AKT/mTOR and RAS/RAF/MAPK pathways and their key phosphorylated kinase alterations in GBMs. This review also discusses potential pharmacological progress from bench work to clinical trials in order to evaluate specific inhibitors as well as therapeutics targeting PI3K and RAS signaling pathways. EXPERT OPINION:Several factors impede clinical progress in targeting GBM, including the high rates of acquired resistance, heterogeneity within and across the tumors, complexity of signaling pathways and difficulty in traversing the blood-brain barrier (BBB). Substantial insight into genetic and molecular pathways and strategies to better tap the potential of these agents include rational combinatorial regimens and molecular phenotype-based patient enrichment, each of which will undoubtedly generate new therapeutic approaches to combat these devastating disabilities in the near future.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Gao Q,Lei T,Ye Fdoi
10.1517/13543784.2013.806484subject
Has Abstractpub_date
2013-08-01 00:00:00pages
1023-40issue
8eissn
1354-3784issn
1744-7658journal_volume
22pub_type
杂志文章,评审abstract:BACKGROUND:Polidocanol is a liquid surfactant having endothelial cell lytic properties. In the form of a controlled, dispensed microfoam it is administered endovenously as a sclerosing agent in the treatment of varicose veins. OBJECTIVE:This review summarizes efficacy of polidocanol endovenous microfoam sclerotherapy ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903376163
更新日期:2009-12-01 00:00:00
abstract::The clinical use of cannabinoids is currently a topic of interest not exclusively, but most importantly, concerning different areas of pain therapy. One of the major obstacles in developing clinically acceptable compounds is the cannabimimetic side-effect profile of delta-9-tetrahydrocannabinol (THC) and other cannabi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780802691951
更新日期:2009-02-01 00:00:00
abstract::Many peptides are synthesised and released from the gastrointestinal tract. Although their roles in the regulation of gastrointestinal function have been known for some time, it has become increasingly evident that they also influence eating behaviour. Peptide YY (PYY) is released postprandially from gastrointestinal ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.5.647
更新日期:2005-05-01 00:00:00
abstract::Of the antiarrhythmic drugs in current use, amiodarone is one of the most effective and is associated with a comparatively low risk of drug-induced pro-arrhythmia, probably due to its multiple pharmacological actions on cardiac ion channels and receptors. However, amiodarone is associated with significant extra-cardia...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.4.415
更新日期:2004-04-01 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:INTRODUCTION:Peripheral arterial disease (PAD) is a manifestation, and marker of severity, of a generalized atherosclerotic process. Antiplatelet therapy is recommended to prevent cardiovascular events but much of the evidence to support this is drawn from studies on older drugs. AREAS COVERED:In this review, the auth...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.974803
更新日期:2014-12-01 00:00:00
abstract:INTRODUCTION:Asthma is a chronic inflammatory disease characterized by bronchial hyper-reactivity. Although many currently available treatment regimens are effective, poor symptom control and refractory severe disease still represent major unmet needs. In the last years, numerous molecular therapeutic targets that inte...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1212838
更新日期:2016-09-01 00:00:00
abstract::Introduction: Renal cell carcinoma (RCC) consists of distinct clinical and biologic entities, with an urgent need for novel therapies targeting histology-specific molecular drivers of cancer growth. The MET pathway is now being targeted by multiple novel agents in clinical development. This review highlights the upcom...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1673366
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND:Age-related macular degeneration is the leading cause of blindness among elderly individuals in industrialized countries. New drugs and advanced concepts for the treatment of dry AMD (dAMD) are needed. A new approach is the application of intravenous infusions of prostaglandin E1. OBJECTIVE:The aim of this ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1517/13543784.2013.794782
更新日期:2013-07-01 00:00:00
abstract::All of the glucose-lowering agents available today for the treatment of diabetes resulted from the in vivo antidiabetic drug discovery approach. This is not surprising given the limited understanding of the biochemical basis of diabetes. With new developments in the elucidation of the biochemistry and physiology of di...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.6.987
更新日期:1998-06-01 00:00:00
abstract::Immunosuppressant drugs are crucial in order to protect transplanted kidney, heart or liver against the body's natural defence mechanisms. These drugs are used to prevent both acute rejection of the organ as well as chronic deterioration of the graft over longer periods of time. Currently used immunosuppressant drugs ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.3.295
更新日期:2005-03-01 00:00:00
abstract::Tuberculosis (TB), which kills more people than any other infectious disease, was declared a global emergency by the World Health Organization in 1993. The emergence of new Mycobacterium tuberculosis strains that are resistant to some or all current antitubercular drugs seriously hampers the control of the disease. Up...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.8.1033
更新日期:2002-08-01 00:00:00
abstract:INTRODUCTION:Sepsis with Bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. Over the past 15 years, recent outbreaks in the US and in Europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1041587
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Gut-specific homing is mainly mediated by the expression of MAdCAM-1 on endothelial cells. An increase in MAdCAM-1 expression has been shown in patients with inflammatory bowel disease (IBD). Areas covered: PF-00547659 is a fully human monoclonal antibody (mAb) toward MAdCAM-1 on endothelial cells, blockin...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1494722
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND:Based partially on encouraging findings from preclinical models, interest has grown in therapeutic inhibition of NF-kappaB to limit inflammatory injury during sepsis. However, NF-kappaB also regulates protective responses, and predicting the net survival effects of such inhibition may be difficult. OBJECTIV...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903018880
更新日期:2009-08-01 00:00:00
abstract::Helicobacter pylori infection causes peptic ulcer disease and must be regarded as a serious infectious disease. Over the past two decades treatment of the infection has been a controversial issue. Treatment is purely empirical and based on combinations of two, three or four existing drugs. Antimicrobial resistance is ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.8.1559
更新日期:2001-08-01 00:00:00
abstract::PDE3 cyclic nucleotide phosphodiesterases are important in cyclic AMP (cAMP) and possibly cyclic GMP-mediated signalling in cardiac and vascular smooth muscle myocytes. Drugs that inhibit these enzymes have inotropic and vasodilatory actions that have proven useful in the short-term treatment of contractile failure an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.11.1529
更新日期:2002-11-01 00:00:00
abstract::Cholesterol can promote inflammation by its ability to stimulate the production of reactive oxygen species that result in the formation of pro-inflammatory oxidised phospholipids. High-density lipoproteins (HDLs) are part of the innate immune response and can be either pro- or anti-inflammatory independently of plasma...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.1.13
更新日期:2006-01-01 00:00:00
abstract::Toll-like receptors (TLRs) form a family of pattern recognition receptors that have emerged as key mediators of innate immunity. These receptors sense invading microbes and initiate the immune response. TLR-mediated inflammation is an important pathogenic link between innate immunity and a diverse panel of clinical di...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.8.857
更新日期:2006-08-01 00:00:00
abstract:INTRODUCTION:The significant proportion of gout patients not reaching serum urate levels below 6.0 mg/dL and the debated pathogenicity of hyperuricemia (HU) itself motivate investigators to develop new drugs to decrease uricemia. AREAS COVERED:This review discusses the drugs considered to be in active development from...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1471133
更新日期:2018-05-01 00:00:00
abstract::Chronic hepatitis B virus (HBV) infection is a major health problem that is responsible for < or = 1 million deaths and 500,000 cases of hepatocellular carcinoma worldwide each year. Drugs that are currently approved by the FDA for the treatment of chronic HBV consist of two groups: the immunomodulators, such as conve...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.10.1277
更新日期:2005-10-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Treatments of pulmonary arterial hypertension (PAH) that have so far proven efficacious are all based on the restoration of endothelium control of pulmonary vascular tone and structure, by administration of prostacyclins, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Howeve...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543781003727099
更新日期:2010-04-01 00:00:00
abstract:INTRODUCTION:Epithelial ovarian cancer (EOC) is the leading cause of gynaecologic cancer death. Although in some cases initial treatment is effective, most of the women diagnosed with EOC will probably need medical treatment for their disease. There is a critical need to develop effective new strategies for the managem...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2013.816282
更新日期:2013-10-01 00:00:00
abstract::Parasitic infections are widespread in developing countries and frequently associated with immunocompromised patients in developed countries. Consequently, such infections are responsible for a significant amount of human mortality, morbidity and economic hardship. A growing consensus has identified the urgent need fo...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.8.957
更新日期:2005-08-01 00:00:00
abstract::Obesity shortens life expectancy and is a risk factor for hypertension and Type 2 diabetes. When added to the standard chow of Sprague-Dawley or Otsuka Long-Evans Tokushima Fatty rats, alpha-lipoic acid (0.5% weight/weight) reduced body weight and food intake. Alpha-lipoic acid also increased whole-body energy expendi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.12.1641
更新日期:2004-12-01 00:00:00
abstract::The topics discussed at this conference covered many aspects of the pathogenesis, epidemiology, diagnosis and treatment of rheumatic diseases, from the search of new therapeutic targets and evaluation of new diagnostic techniques to preclinical and clinical development of novel therapies. This contribution focuses pri...
journal_title:Expert opinion on investigational drugs
pub_type:
doi:10.1517/13543784.12.10.1713
更新日期:2003-10-01 00:00:00
abstract::IL-5 is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of Th-2 cells leads to the production of IL-5. The pro-eosinophilic effects of IL-5 include: (1) enhanced replication and differentiation of eosinophilic myelocytes; (2) enhanced degranulation of eosi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.3.491
更新日期:2000-03-01 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:IMPORTANCE OF THE FIELD:Contrasting with the broad activation of the PI3K/AKT/mammalian target of rapamycin (mTOR) survival pathway in most cancer, activity of rapalogues appears to be restricted to a few tumor types. AREAS COVERED IN THIS REVIEW:The analysis of molecular activity of the PI3K/AKT/mTOR pathway and resi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.499121
更新日期:2010-08-01 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