Abstract:
INTRODUCTION:Fibroblast growth factor receptors (FGFR 1-4) are a highly conserved family of receptor tyrosine kinases, involved in several physiological processes. Genetic aberrations of FGFRs and their ligands, fibroblast growth factors (FGFs) are involved in several pathological processes including cancer. The FGF-FGFR axis has emerged as a treatment target in oncology. Because these aberrations drive cancer progression, the development of FGFR targeted therapies have been accelerated. AREAS COVERED:In this comprehensive review, we evaluate molecular pathology and targeted therapies to FGFRs. We reviewed the evidence for safety and efficacy from preclinical and clinical studies (phase I-III) of FGFR targeted therapies. We also discuss potential challenges in bringing these targeted therapies from bench to bedside and the potential opportunities. EXPERT OPINION:Despite the challenges of the clinical development of FGFR targeted therapies, two FGFR small-molecule inhibitors, namely Erdafitinib and Pemigatinib, are FDA approved for urothelial cancer and cholangiocarcinoma, respectively. Understanding and detection of FGFR genomic aberrations, protein overexpression and the development of isoform-specific inhibitors are factors in the clinical success of these therapies. An enhanced understanding of patient selection based on a gene signatures or biomarkers is key to success of FGFR targeted therapies.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Chandana SR,Babiker HM,Mahadevan Ddoi
10.1080/13543784.2020.1838484subject
Has Abstractpub_date
2020-12-01 00:00:00pages
1413-1429issue
12eissn
1354-3784issn
1744-7658journal_volume
29pub_type
杂志文章abstract::In the last three years, most efforts of virologists and immunologists involved in the field of HIV have been focussed on strategies aimed at eradicating the infection. So far, however, all attempts have been unsuccessful. Indeed, even if the currently available potent antiretroviral regimens are able to induce a prof...
journal_title:Expert opinion on investigational drugs
pub_type: 社论
doi:10.1517/13543784.9.2.193
更新日期:2000-02-01 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that can lead to permanent disability and deformity. Despite current treatment modalities, many patients are still unable to reach remission. Interleukin-1 receptor-associated kinase 4 (IRAK-4) inhibitors are novel agents designed to s...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2020.1752660
更新日期:2020-05-01 00:00:00
abstract::Two classes of luteinising hormone-releasing hormone (LHRH) analogues have been developed so far to be used for oncological therapies: LHRH agonists and antagonists. LHRH agonists are widely and successfully used for the management of steroid-dependent malignancies. Chronic administrations of these compounds result in...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.4.709
更新日期:2001-04-01 00:00:00
abstract::Early breast carcinoma is defined as pathological stage 1 (pT1N0M0) tumour and its incidence has recently increased possibly due to the advent of mammography based mass screening. Overall survival of these patients is in general excellent, but more than 20% of them will eventually develop distant metastasis and die. T...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543781003718833
更新日期:2010-04-01 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::Gossypol has received significant attention as a result of its potential therapeutic application as a male antifertility agent. Furthermore, recent research examining the biological activity of gossypol has revealed a number of other promising lines of enquiry. These have focused on the antitumour, antiviral and antio...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.11.1419
更新日期:2005-11-01 00:00:00
abstract:INTRODUCTION:Therapeutic options for mycosis fungoides and Sézary syndrome include a variety of immunomodulatory, epigenetic, and cytotoxic options; however, none has been demonstrated to be efficacious for all patients, or to deliver deep and durable responses to the majority of patients. In this review, we examine th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1498081
更新日期:2018-08-01 00:00:00
abstract::After thousands of years of interest the last few decades have seen a huge increase in our knowledge of the cannabinoids and their mode of action. Their potential as medical therapeutics has long been known. However, very real concerns over their safety and efficacy have lead to caution and suspicion when applying the...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.10.1365
更新日期:2002-10-01 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::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:GLP-1 receptor agonists have been shown to be effective in the treatment of type 2 diabetes mellitus (T2DM). Although the first GLP-1 receptor agonist, exenatide, was approved in the mid-2000s, other agents with longer durations of action (that do not require twice-daily dosing) are now being developed. In...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.638282
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:Approximately 300 million people worldwide are currently affected by asthma. Improvements in the understanding of the mechanisms involved in such inflammatory airway disorders has led to the recognition of new therapeutic approaches. Heparin, a widely used anticoagulant, has been shown to be beneficial in ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.866092
更新日期:2014-03-01 00:00:00
abstract::In addition to a variety of other novel agents, interest in histone deacetylase inhibitors (HDACIs) as antineoplastic drugs has recently accelerated and increasing numbers of these compounds have entered clinical trials in humans. HDACIs represent a prototype of molecularly targeted agents that perturb signal transduc...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.1.21
更新日期:2004-01-01 00:00:00
abstract::Female hormonal contraceptive methods have undergone slow change over the past four decades. Due to social, political and legal reasons, as well as medical complications, several new methods have been removed from the contraceptive armamentarium almost as quickly as they have been added. With worldwide unintended preg...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.14.4.449
更新日期:2005-04-01 00:00:00
abstract:INTRODUCTION:Sorafenib is an oral multikinase inhibitor with anti-angiogenic and anti-proliferative activity that is indicated for use in hepatocellular and renal cell carcinomas. Sorafenib is being developed in a number of solid tumors, including breast cancer (BC). AREAS COVERED:A series of four randomized, double-b...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.689824
更新日期:2012-08-01 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::ATP-gated P2X7 receptors (P2X7) make a unique family of extracellular ATP-activated plasma membrane ion channels expressed in haematopoietic and epithelial cells. They have been extensively studied in immune cells where their activation leads to the rapid release of pro-inflammatory cytokines and the initiation of the...
journal_title:Expert opinion on investigational drugs
pub_type: 社论
doi:10.1517/13543784.2011.583918
更新日期:2011-07-01 00:00:00
abstract::The vasopressin system is complex and interacts with the central nervous, cardiovascular, renal, and hematological systems. Vasopressin plays an important role in the control of blood osmolarity and vascular tone, but is also involved in many other physiological events, which are mediated mainly via three types of vas...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903066764
更新日期:2009-08-01 00:00:00
abstract:INTRODUCTION:Aberrant regulation of platelet-derived growth factors (PDGFs) and their receptors (PDGFR) has been shown to be involved in many solid tumors, including breast cancer. PDGFR-α and PDGFR-β expressions were documented in breast cancer and are correlated with tumor aggressiveness and metastasis. Preclinical e...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.895323
更新日期:2014-05-01 00:00:00
abstract:INTRODUCTION:Glioblastoma is a primary brain tumor with a poor prognosis despite multimodal therapy including surgery, radiotherapy and alkylating chemotherapy. Novel therapeutic options are therefore urgently needed; however, there have been various drug failures in late-stage clinical development. The proteasome repr...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1803827
更新日期:2020-10-01 00:00:00
abstract:INTRODUCTION:There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infect...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1005205
更新日期:2015-03-01 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: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 an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.632408
更新日期:2012-01-01 00:00:00
abstract::New bolus fibrinolytic agents derived from the recombinant human tissue plasminogen activator (t-PA) have emerged as a new means of dissolution of the occlusive thrombosis associated with acute myocardial infarction. Lanoteplase is a fibrinolytic drug derived from t-PA by deleting its fibronectin finger-like and epide...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.11.2689
更新日期:2000-11-01 00:00:00
abstract:INTRODUCTION:Soft tissue sarcomas (STS) are a rare and difficult to treat malignancy. Efforts to utilize targeted therapy have been ongoing for the last decade and have resulted in the approval of pazopanib for treatment of advanced disease. Although several other agents have been investigated, the inability to predict...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1076792
更新日期:2015-01-01 00:00:00
abstract::Leukotriene B(4) (LTB(4)) is a lipid inflammatory mediator derived from membrane phospholipids by the sequential actions of cytosolic phospholipase A2 (PLA2), 5-lipoxygenase (5-LO) and leukotriene A(4) (LTA(4)) hydrolase. Several inflammatory diseases, including asthma, chronic obstructive pulmonary disease, arthritis...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.12.1909
更新日期:2007-12-01 00:00:00
abstract:INTRODUCTION:Stroke is the second leading cause of death worldwide and the leading cause of adult neurological disability. Despite advances in stroke unit care, and increasing use of thrombolysis, there remains an urgent need for safe and effective treatments for acute ischaemic stroke. However, this is against a backd...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1020110
更新日期:2015-05-01 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::The association of abnormalities in the cellular and humoral immune system with various autoimmune diseases provides the rationale for apheresis technologies. While plasmapheresis or plasma exchange is limited by its non-selective removal of all plasma components, modern apheresis techniques aim to provide more specif...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.9.2017
更新日期:2000-09-01 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