Abstract:
INTRODUCTION:Various trials have attempted to develop gene expression profiles (GEPs) that may provide a better predictor of clinical outcome over traditional clinicopathological criteria. AREAS COVERED:The review focuses on two main areas: trials examining chemotherapy-induced GEP changes pre- and post-treatment, and studies correlating baseline signatures with chemosensitivity. In the first part of the article, the authors specifically cover areas pertaining to general/drug-specific tumor GEP changes and GEP changes between responders versus non-responders in specific molecular subclasses. The authors also discuss non-tumor-specific signatures, and provide a comparison of different biopsy methods. The authors also discuss the challenges that must be overcome in this area, looking at the clinical application of gene expression profiling and some of the multigene assays which have gained clinical utility. EXPERT OPINION:Current studies are challenged by a number of issues including: small sample sizes, retrospective analyses, varying chemotherapy regimens and response end points, the need for fresh frozen samples, distinct gene signatures in multiple platforms with minimal overlap and inherent microarray technological complexities. To date, no pharmacogenomic drug-specific predictor has been implemented clinically. Future studies should focus on distinct molecular subgroups by pooling resources and validation in well-powered randomized trials. Incorporating GEPs with newer biotechnological modalities may provide a more robust predictive model.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Tan SH,Lee SCdoi
10.1517/17425255.2012.694867subject
Has Abstractpub_date
2012-09-01 00:00:00pages
1083-113issue
9eissn
1742-5255issn
1744-7607journal_volume
8pub_type
杂志文章,评审abstract:INTRODUCTION:Iron overload is an inevitable consequence of transfusion therapy for a variety of underlying anemias. Iron overload, without effective chelation, will lead to significant morbidity and mortality. Deferasirox (Exjade®) is an oral tridentate iron chelator used for reducing iron overload. AREAS COVERED:In a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.640674
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Obesity, hypertension and Type 2 diabetes are major contributing factors to the increase in the number of patients that have chronic kidney disease. The clustering of visceral obesity and cardiovascular risk factors has been designated metabolic syndrome or cardiometabolic syndrome. Cardiometabolic syndrome ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.2.165
更新日期:2008-02-01 00:00:00
abstract:INTRODUCTION:Emtricitabine/tenofovir disoproxil fumarate fixed-dose combination (FTC/TDF FDC) is the co-formulation of a nucleoside and a nucleotide, respectively. After oral administration, both drugs exhibit plasma and intracellular half-lives suitable for once-daily dosing. Within the host cells, active metabolites ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.714367
更新日期:2012-10-01 00:00:00
abstract:INTRODUCTION:Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy. However, ∼ 30% of patients do not remain seizure free. It is possible that methylxanthine derivatives (e.g., caffeine and theophylline) may partially account for this outcome. AREAS COVERED:Data on the convulsive activity of methylx...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.920822
更新日期:2014-07-01 00:00:00
abstract::Toxicogenomics is the application of gene expression profiling technology to toxicology. This results in the generation of very large and complex gene expression data sets associated with the development of toxicities. It is widely assumed that this data can be deconvoluted to reveal novel insights into toxicological ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.2.247
更新日期:2005-08-01 00:00:00
abstract:INTRODUCTION:In vitro genotoxicity assays have a high sensitivity to detect rodent carcinogens, but mammalian cell tests have a propensity for misleading positive results (poor specificity). Recent data show a greater risk of misleading positive results in p53-deficient rodent cell lines than in p53-competent human cel...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.627855
更新日期:2011-12-01 00:00:00
abstract:INTRODUCTION:Over the past decade, zebrafish have been tasked to play important roles from modeling human diseases to finding cures for them. Inadvertently, these fish now find themselves swimming along the drug development pipeline. A number of studies have been conducted to see if these small fish are up to the task ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.562197
更新日期:2011-05-01 00:00:00
abstract:INTRODUCTION:Integration of targeted therapy and additional chemotherapy options has improved median overall survival (OS) in patients with unresectable metastatic colorectal cancer (mCRC). Cetuximab and panitumumab are examples of targeted therapies, specifically against the epidermal growth factor receptor (EGFR). Th...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1112787
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy accounting for a significant percentage of thyroid cancer-related fatal events. Traditional treatment modalities used in the other types of thyroid carcinomas have been proved largely ineffective in advanced MTC. Better understanding of the m...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.885015
更新日期:2014-03-01 00:00:00
abstract:INTRODUCTION:Obesity is an epidemic associated with significant morbidity. Lorcaserin , a novel serotonin 2C receptor antagonist, was recently approved as an adjunct to lifestyle modification for long-term weight loss and maintenance. Clinical studies in patients without diabetes demonstrated 5.8% mean weight loss from...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.798643
更新日期:2013-08-01 00:00:00
abstract:INTRODUCTION:A more concentrated insulin glargine formulation, containing 300 U/mL (Gla-300) was approved in 2015 in the US and Europe for the treatment of diabetes mellitus in adults. AREAS COVERED:This drug evaluation focuses on the pharmacokinetics (PK) and pharmacodynamics (PD) of Gla-300 from studies published up...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1202916
更新日期:2016-08-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The prevalence of acute renal allograft rejection has decreased substantially in past decades due to new and more specific immunosuppressive compounds but improvements in long-term graft function have not been achieved. There is a large need for new immunosuppressive agents that lack toxicity of...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.540238
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Approaches aiming to model the time course of tumor growth and tumor growth inhibition following a therapeutic intervention have recently been proposed for supporting decision making in oncology drug development. When considered in a comprehensive model-based approach, tumor growth can be included in the c...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.693480
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:Cytochrome P450 2E1 (CYP2E1) plays a central role in the metabolism and metabolic activation of a large number of small, mostly xenobiotic compounds. These qualities distinguish CYP2E1 from traditional enzymes and pose significant challenges to understanding the role and consequences of CYP2E1-mediated metab...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.8.1053
更新日期:2008-08-01 00:00:00
abstract::Extensive growth in the field of molecular biology in recent decades has led to the development of new and powerful experimental and computational tools that enable the analysis of complex biological responses to chemical exposure on both a functional and structural genetic level. The ability to profile global respons...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.11.1379
更新日期:2008-11-01 00:00:00
abstract:INTRODUCTION:The fixed-dose combination of three direct-acting antivirals (DAA), namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single tablet regimen developed for the treatment of HCV infection. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1359254
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:Painful diabetic neuropathy (PDN) is a disabling pain condition. Its pathomechanism remains unknown, but a sensitization and neuronal hyperexcitabilty have been suggested. Only symptomatic pharmacological pain management treatment is currently available. AREAS COVERED:The origin of PDN is enigmatic, and t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1184648
更新日期:2016-07-01 00:00:00
abstract:INTRODUCTION:Omalizumab is a subcutaneously administrated monoclonal anti-IgE antibody indicated in adults, adolescents and children 6 years of age and older with moderate to severe allergic asthma uncontrolled by conventional pharmacological treatments and sensitization to at least one perennial allergen. Area covered...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1248403
更新日期:2016-12-01 00:00:00
abstract:INTRODUCTION:It is widely accepted that current practice of polypharmacy inevitably increases the incidence of drug-drug interactions (DDIs). Serious DDIs are a major liability for new molecular entities entering the pharmaceutical market. Various strategies are employed to avoid problematic compounds for clinical deve...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1013095
更新日期:2015-04-01 00:00:00
abstract:INTRODUCTION:Drug-disease interactions include the impact of a drug and a particular disease condition on each other. However, the current practice in addressing drug-disease interaction is unbalanced and mostly limited to how the drug worsens the disease or health condition. AREAS COVERED:Aspirin and gastric ulcer in...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1201064
更新日期:2016-09-01 00:00:00
abstract:INTRODUCTION:Chemoprevention of cancer refers to the use of natural or synthetic compounds to abolish or perturb a variety of steps in tumor initiation, promotion, and progression. This can be realized through different mechanisms, including activation of free radical scavenging enzymes, control of chronic inflammation...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2021.1839412
更新日期:2021-01-01 00:00:00
abstract:INTRODUCTION:This meeting report presents a brief summary on the 4th Annual Predictive Toxicology Summit 2012, which was held on 15 - 16 February 2012 in London. AREAS COVERED:The majority of presentations came from global pharmaceutical companies, although small and medium enterprise (SME) and academic researchers we...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1517/17425255.2013.802306
更新日期:2013-08-01 00:00:00
abstract:INTRODUCTION:The fixed-dose combination therapy of sofosbuvir (SOF) plus velpatasvir (VEL) is the first pangenotypic, direct-acting antiviral (DAA), single-treatment regimen (STR) for the treatment of hepatitis C virus (HCV) infection to be commercialized. It is approved for the treatment of HCV genotypes 1, 2, 3, 4, 5...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1292253
更新日期:2017-04-01 00:00:00
abstract:INTRODUCTION:Despite initial patient benefit, drug resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) is inevitable. One of the key mechanisms responsible for the development of acquired drug resistance is the secondary T790M missense mutation in exon 20 of the EGFR kinase domain. Afatinib is an ATP-...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.832755
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:5-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the treatment of UC. OBJECTIVE:To summarize current data on balsalazide and to discuss its impact on management of UC. METHODS:A systematic review o...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903206996
更新日期:2009-10-01 00:00:00
abstract:INTRODUCTION:Boceprevir is an NS3/NS4A serine protease inhibitor that was approved for use in Hepatitis C virus (HCV) genotype 1 patients by the US Food and Drug Administration (FDA) in May 2011. The approval of this protease inhibitor marked a major paradigm shift in the treatment of HCV, as it was one of the first of...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.840290
更新日期:2013-12-01 00:00:00
abstract:INTRODUCTION:. Membrane transporters are integral to the maintenance of cellular integrity of all tissue and cell types. While transporters play an established role in the systemic pharmacokinetics of therapeutic drugs, tissue specific expression of uptake transporters can serve as an initiating mechanism that governs ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2020.1755253
更新日期:2020-06-01 00:00:00
abstract:INTRODUCTION:multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclon...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1417388
更新日期:2018-01-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Cytochrome (CYP) P450 is a collective name for a very large group of heme enzymes, which catalyze largely oxidative reactions, including those of pharmacological and toxicological importance. Their efficient operation requires coupling of specific electron donor and O(2) consumption and substrat...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903329095
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Extensive within-population variability is the essence of neonatal pharmacology. Despite this, infants remain one of the last therapeutic orphans. Together with additional legal initiatives, tailoring of already available tools (modeling, covariates, pharmacovigilance) may significantly improve pharmacothe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.931937
更新日期:2014-08-01 00:00:00