Abstract:
INTRODUCTION:Despite recent advances, pulmonary arterial hypertension (PAH) remains a devastating disease which harbors a poor prognosis. Novel therapeutic approaches directly targeting pulmonary vascular remodeling are warranted. AREAS COVERED:This review delineates the current limitations in the management of PAH and focuses on a novel, anti-proliferative therapeutic concept. It will help readers understand the mechanisms of receptor tyrosine kinase signaling, with a special focus on platelet-derived growth factor (PDGF) receptors and their role in the pathobiology of PAH. Furthermore, it provides a comprehensive summary regarding the rationale, efficacy and safety of the tyrosine kinase inhibitor imatinib mesylate , which potently inhibits the PDGF receptor, as an additional treatment option in PAH. EXPERT OPINION:PDGF is a potent mitogen for pulmonary vascular smooth muscle cells and represents an important mediator of pulmonary vascular remodeling. Imatinib mesylate, a compound that inhibits the Bcr-Abl kinase and was developed for the treatment of chronic myeloid leukemia, also targets PDGF receptors. Both experimental and clinical data indicate that it reverses the vascular remodeling process even when it is fully established. Results from Phase II and III clinical trials suggest potent and prolonged efficacy in patients with severe PAH (i.e., pulmonary vascular resistance > 800 dynes*s*cm(-5)). Future studies should evaluate the long-term clinical efficacy and safety of imatinib, including patients with less impaired hemodynamics. Based on the current knowledge, this compound is likely to become an additional treatment option for patients with PAH and has the potential to at least partially correct the pathology of the disease.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
ten Freyhaus H,Dumitrescu D,Berghausen E,Vantler M,Caglayan E,Rosenkranz Sdoi
10.1517/13543784.2012.632408subject
Has Abstractpub_date
2012-01-01 00:00:00pages
119-34issue
1eissn
1354-3784issn
1744-7658journal_volume
21pub_type
杂志文章,评审abstract::Standard drug therapy of adult polymyositis, dermatomyositis and inclusion body myositis includes high-dose corticosteroids and cytotoxic drugs (methotrexate, azathioprine (AZA) and cyclophosphamide). Recent data are in favour of the early introduction of a cytotoxic or immunomodulating drug in addition to corticoster...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.7.1265
更新日期:2001-07-01 00:00:00
abstract::Since the introduction of the first through the skin (TTS) therapeutic in 1980, a total of 34 TTS products have been marketed and numerous drugs have been tested by more than 50 commercial organisations for their suitability for TTS delivery. Most of the agents which have been tested have had low molecular weights, du...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.12.1887
更新日期:1997-12-01 00:00:00
abstract::Aripiprazole has made a significant contribution to the treatment of schizophrenia and related disorders with an improved safety and tolerability profile, which has been attributed to its unique pharmacological profile. It has been claimed that partial agonism of the dopamine D(2) and 5-HT(1A) receptors and antagonism...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.6.771
更新日期:2007-06-01 00:00:00
abstract::Type 2 diabetes is a chronic metabolic disease that adversely affects both the quality and longevity of life. The disease is characterised by elevated blood glucose (hyperglycaemia) that is associated with microvascular complications and increased macrovascular risk. Existing oral agents, either alone or in combinatio...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.2.145
更新日期:2008-02-01 00:00:00
abstract::The deposition of a platelet rich thrombus on an atherosclerotic plaque is a critical step in the development of unstable coronary syndromes. Currently available therapeutic agents such as aspirin and ticlopidine are relatively weak inhibitors of platelet aggregation. Recently, antagonists to platelet glycoprotein IIb...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.9.1257
更新日期:1997-09-01 00:00:00
abstract:INTRODUCTION:Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast ca...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1299707
更新日期:2017-04-01 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::The failure of drug candidates in clinical development remains a critical issue for the pharmaceutical and biotechnology industries. This article documents those oncology drugs discontinued in 2008 and briefly reviews reasons for termination of development. Source information was derived from a search of the Pharmapro...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543780903151806
更新日期:2009-11-01 00:00:00
abstract::Overactive bladder (OAB) is a chronic distressing condition characterised by urinary urgency with or without urge incontinence, usually with frequency (voiding at least eight times daily) and nocturia. It affects millions of people worldwide independent of age, sex and race. The prevalence increases with age and is re...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.9.1017
更新日期:2006-09-01 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::The principal components of the asthmatic response are airways hyper-responsiveness, persistent inflammation and mucus hypersecretion. Although these components are inter-related, any of these can predominate at different times and for different patients and each requires a different approach to therapy. As a result o...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.6.889
更新日期:2007-06-01 00:00:00
abstract::Introduction: Osteoarthritis (OA) is the most common form of arthritis. Knee OA is associated with joint pain, activity limitation, physical disability, reduced health-related quality of life, and increased mortality. To date, all pharmacologic treatments for OA are directed toward pain management. Lorecivivint (LOR) ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1842357
更新日期:2020-12-01 00:00:00
abstract::In order to improve therapy and increase the quality of life for diabetic patients, it has been of significant interest to develop rapid-acting insulin preparations that mimic the physiological meal-time profile of insulin more closely than soluble human insulin. Insulin aspart (B28Asp human insulin) is a novel rapid-...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.9.1431
更新日期:1999-09-01 00:00:00
abstract::Carvedilol is a beta-blocker with ancillary properties. Pilot clinical studies with carvedilol, added to the standard therapy of digoxin, diuretics and ACE inhibitors, showed beneficial effects in mild, moderate and severe heart failure. Patients consistently showed improvement in LV ejection fraction and NYHA functio...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.5.971
更新日期:2001-05-01 00:00:00
abstract:INTRODUCTION:Noise-induced hearing loss (NIHL) due to industrial, military, and recreational noise exposure is a major, but also potentially preventable cause of acquired hearing loss. For the United States it is estimated that 26 million people (15% of the population) between the ages of 20 and 69 have a high-frequenc...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1269171
更新日期:2017-01-01 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:INTRODUCTION:Ewing sarcoma family tumors (ESFT) are a group of aggressive diseases, characterized histologically by small, round, blue cells and genetically by translocation involving EWS and ETS partner genes. The current treatment of localized Ewing sarcoma (ES) requires a multi-disciplinary approach, including multi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2016.1168398
更新日期:2016-06-01 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::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::Zolmitriptan is a new oral acute treatment for migraine. It is a selective and potent agonist at the serotonin (5-HT)(1B/1D) receptor and was developed to improve on the oral bioavailability, tissue selectivity and CNS penetration of earlier compounds. Animal studies confirmed that these objectives had been attained. ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.4.633
更新日期:1998-04-01 00:00:00
abstract::Biologically-based skin substitutes have developed as commercial products over the last 5 years. The first generation includes the collagen-based synthetic device, Integra, and Alloderm, which is based on devitalised and cross-linked human dermis. These are used as dermal replacements for third degree burns. Within th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.5.803
更新日期:1998-05-01 00:00:00
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:INTRODUCTION:Metastases to the central nervous system are the most common cause of malignant intracranial tumors in adults. Current standard of care includes surgery and radiation, but overall survival remains poor. A range of systemic therapies are emerging as promising treatment options for these patients. AREAS COV...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1836154
更新日期:2020-12-01 00:00:00
abstract::Introduction: The armamentarium of antileishmanial drugs is small. It is further being threatened by the development of resistance and decreasing sensitivity to the available drugs. The development of newer drugs is sorely needed. Areas covered: The authors have based their review on a literature search performed usin...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.2014.954035
更新日期:2015-01-01 00:00:00
abstract::Methylphenidate (MPH) is one of the most commonly prescribed medications to treat attention deficit hyperactivity disorder (ADHD). Despite the elevated rates of ADHD in children with epilepsy, few studies have examined the use of MPH in this population. Case reports have warned about new-onset seizures in patients tre...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.1.77
更新日期:2008-01-01 00:00:00
abstract::Increasing evidence suggests an important role for autocrine/paracrine prolactin in breast and prostate cancers and other disease states. Prolactin production in these extrapituitary sites is not governed by dopamine agonists, a finding that has spurred the production of prolactin receptor antagonists. This review foc...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.10.1257
更新日期:2006-10-01 00:00:00
abstract:INTRODUCTION:The purpose of this article is to highlight novel therapies that are being used in scleroderma (SSc). Therapeutic interventions in SSc generally target at least one of three ongoing biological processes characteristic of the disease: vasculopathy, autoimmunity and tissue fibrosis. Treatment decisions in SS...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.848852
更新日期:2014-02-01 00:00:00
abstract::Introduction: Plasma kallikrein is a mediator of vascular leakage and inflammation. Activation of plasma kallikrein can induce features of diabetic macular edema (DME) in preclinical models. Human vitreous shows elevated plasma kallikrein levels in patients with DME. Because of the incomplete response of some patient...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2020.1723078
更新日期:2020-03-01 00:00:00
abstract::With the current standard chemotherapy regimens only approximately 25% of acute myelogenous leukaemia (AML) patients survive > 5 years. Aurora kinases are overexpressed in many human cancers. VX-680 inhibited Aurora-A, -B, -C and the FMS-like tyrosine kinase-3 with apparent inhibitory constants of 0.6, 18, 4.6 and 30 ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.9.1199
更新日期:2004-09-01 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