Abstract:
INTRODUCTION:Frontline chemotherapy is successful against chronic lymphocytic leukemia (CLL), but results in untoward toxicity. Further, prognostic factors, cytogenetic anomalies, and compensatory cellular signaling lead to therapy resistance or disease relapse. Therefore, for the past few years, development of targeted therapies is on the rise. PI3K is a major player in the B-cell receptor (BCR) signaling axis, which is critical for the survival and maintenance of B cells. Duvelisib, a PI3K δ/γ dual isoform specific inhibitor that induces apoptosis and reduces cytokine and chemokine levels in vitro, holds promise for CLL. Areas covered: Herein, we review PI3K isoforms and their inhibitors in general, and duvelisib in particular; examine literature on preclinical investigations, pharmacokinetics and clinical studies of duvelisib either as single agent or in combination, for patients with CLL and other lymphoid malignancies. Expert opinion: Duvelisib targets the PI3K δ isoform, which is necessary for cell proliferation and survival, and γ isoform, which is critical for cytokine signaling and pro-inflammatory responses from the microenvironment. In phase I clinical trials, duvelisib as a single agent showed promise for CLL and other lymphoid malignancies. Phase II and III trials of duvelisib alone or in combination with other agents are ongoing.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Vangapandu HV,Jain N,Gandhi Vdoi
10.1080/13543784.2017.1312338subject
Has Abstractpub_date
2017-05-01 00:00:00pages
625-632issue
5eissn
1354-3784issn
1744-7658journal_volume
26pub_type
杂志文章,评审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::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::Introduction: Neuropathic pain is a chronic condition that significantly affects the quality of life of millions of people globally. Most of the pharmacologic treatments currently in use demonstrate modest efficacy and over half of all patients do not respond to medical management. Hence, there is a need for new, effi...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2020.1728254
更新日期:2020-03-01 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: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: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::Introduction: A compound that simultaneously inhibits PDE3 and PDE4 should increase airway caliber by relaxing the smooth muscle and, simultaneously, suppress airway inflammatory responses. Ensifentrine (RPL554) is considered a PDE3/4 inhibitor, although its affinity for PDE3 is 3,440 times higher than that for PDE4, ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1661990
更新日期:2019-10-01 00:00:00
abstract::Urinary tract infections (UTIs) are one of the most common reasons people seek medical attention. There are > 50% of women who will have at least one UTI during their lifetime and most of these will require a physician visit and antibiotic treatment. The high prevalence continues to the in-patient setting where genito...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.5.519
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Acute decompensated heart failure (ADHF) is associated with increased hospitalization rates and high in-hospital mortality, and has emerged as a major public health problem over the past decade. In recent years, several new drugs and therapeutic approaches have failed to reduce short- and long-term morbidity...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780902922660
更新日期:2009-06-01 00:00:00
abstract:INTRODUCTION:Tetomilast is a novel thiazole phosphodiesterase-4 (PDE-4) inhibitor, which may prove useful in both the treatment of inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD). Here, the authors review the pharmacology of the drug, and offer critical review of the available data for...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.732065
更新日期:2012-12-01 00:00:00
abstract::AGI-1067 is a derivative of probucol that is a promising new development for the treatment of restenosis and possibly atherosclerosis. In monkeys fed a high-fat diet for 1 year, AGI-1067 prevented the development of atherosclerosis. In these monkeys, AGI-1067 lowered plasma levels of low-density lipoprotein (LDL)-chol...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.11.1855
更新日期:2003-11-01 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::Cyclooxygenase-2 (COX-2) is constitutively expressed in the central nervous system, and is thought to have an important functional role therein. COX-2 interacts with neurotransmitters such as acetylcholine, 5-hydroxytryptamine and glutamate but is also involved in the regulation of the central nervous system immune sy...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.8.1033
更新日期:2004-08-01 00:00:00
abstract::Introduction: Cyclin-dependent kinase 7 (CDK7) is a part of the CDK-activating kinase family (CAK) which has a key role in the cell cycle and transcriptional regulation. Several lines of evidence suggest that CDK7 is a promising therapeutic target for cancer. CDK7 selective inhibitors such as SY-5609 and CT7001 are in...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2021.1850693
更新日期:2021-01-01 00:00:00
abstract::Diminished efficacy in terms of clinical relapses and lesion load on magnetic resonance images for patients developing neutralising antibodies (NAbs) to recombinant IFN-beta may be found in multiple sclerosis. NAbs become detectable over the first few years of therapy, disappearing during the treatment course in some ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.7.1153
更新日期:2003-07-01 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:UNLABELLED:IMPORTANCE OF THIS FIELD: Microtubule-inhibiting drugs are among the most commonly prescribed agents in the combat against cancer, though the clinical use of these drugs is limited by acquired resistance, risk of hypersensitivity reactions and intolerable toxicity. With progress in our understanding of cytos...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903571631
更新日期:2010-03-01 00:00:00
abstract:INTRODUCTION:Inhaled corticosteroids are the only drugs that effectively suppress the airway inflammation, but they can induce considerable systemic and adverse effects when they are administered chronically at high doses. Consequently, the pharmaceutical industry is still searching for newer entities with an improved ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1078310
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Erectile function is an important aspect in the quality of life of many men. For men with erectile dysfunction (ED), a spectrum of treatment options exists. Novel therapies for ED are currently being developed in order to delay surgical placement of a penile prosthesis - the final step in the management of...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1324570
更新日期:2017-06-01 00:00:00
abstract::The tremendous increase in the global prevalence of Type 2 diabetes (T2D) and its conglomeration of metabolic disorders has dramatically intensified the search for innovative therapies to fight this emerging epidemic. Over the last decade, the family of nuclear receptors, especially the peroxisome proliferator-activat...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.7.763
更新日期:2006-07-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Irritable bowel syndrome (IBS) represents one of the most common gastrointestinal disorders, with the diarrhea-predominant form (D-IBS) representing an area of high unmet medical need. One difficulty in identifying suitable treatments for IBS is that although there are animal models for the comp...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.515209
更新日期:2010-10-01 00:00:00
abstract::Improving the tumour selectivity of cytotoxic drugs through conjugation to tumour-reactive monoclonal antibodies may lead to novel, more potent agents for cancer therapy. The maytansinoid drugs are 100- to 1000-fold more cytotoxic in vitro than current clinical anticancer drugs. We recently demonstrated that conjugati...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.2.169
更新日期:1997-02-01 00:00:00
abstract:INTRODUCTION:Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the two complications of diabetes that cause visual loss and blindness. Laser photo-coagulation in the past was used to prevent progression of disease to these advanced stages. Advances in pathophysiologic understanding of DME an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1201062
更新日期:2016-09-01 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: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:INTRODUCTION:Available drugs partially attenuate the hyperglycemia characteristic of diabetes. However, successful approaches to treat the root cause or to cure or prevent diabetes remain elusive. Drug discovery and development programs continue to focus on mechanisms that impact specific symptoms of diabetes. In 2014,...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.2015.1058777
更新日期:2015-01-01 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::Colorectal cancer is one of the most common cancers worldwide. Through well-designed clinical trials, advances have been made in the treatment of localised and advanced colorectal cancer. It has been established that 6 months of 5-fluorouracil-based chemotherapy will improve overall survival in patients with stage III...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.6.871
更新日期:2002-06-01 00:00:00
abstract::The introduction of HIV-1 protease inhibitors in 1995 ushered in the era of highly active antiretroviral therapy. For the first time, inhibition of two key enzymes responsible for HIV replication, reverse transcriptase and protease, was possible. The combination of two nucleoside reverse transcriptase inhibitors with ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.9.1295
更新日期:2002-09-01 00:00:00
abstract::Marfan syndrome is the most common genetic disorder of the connective tissue with an estimated prevalence of 1:10,000. The disease is characterised by manifestations in the cardiovascular, skeletal and ocular systems. The most severe manifestations are those of the cardiovascular system: mitral valve prolapse and dila...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.7.983
更新日期:1999-07-01 00:00:00