Abstract:
IMPORTANCE OF THE FIELD:There has been much interest in generating gene signatures to predict treatment response in breast cancer. AREAS COVERED IN THIS REVIEW:There are at least 15 published studies that describe baseline tumor gene signatures predicting chemotherapy sensitivity. As an extension of these baseline studies, there have been at least 8 published studies evaluating chemotherapy-induced tumor genomic changes over time in human breast cancers. WHAT THE READER WILL GAIN:Studies on chemotherapy-induced gene expression changes were reviewed in detail. Drug-induced biological changes within the tumor shed light on mechanisms of drug resistance and provided valuable insights regarding genes and pathways that were regulated by different drugs, including therapeutic targets that could be exploited to overcome resistance. One study also suggested post-chemotherapy gene signatures to be more predictive of response and survival than the unchallenged baseline signatures. TAKE HOME MESSAGE:Studies on chemotherapy-induced changes, although informative, are logistically demanding to execute, often with significant attrition of collected samples resulting in small datasets. They are further limited by heterogeneity of study population, chemotherapy regimens used, timing of the post-therapy sample and definition of response endpoint, making cross-comparisons of studies and data interpretation difficult. Future studies should address these limitations, and should involve larger sample sets and prospective studies for validation.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Tan SH,Lee SCdoi
10.1517/17425250903510611subject
Has Abstractpub_date
2010-03-01 00:00:00pages
283-306issue
3eissn
1742-5255issn
1744-7607journal_volume
6pub_type
杂志文章,评审abstract:INTRODUCTION:Nucleosidic analogs such as pyrimidine and purine derivatives are mainstay in the field of treating cancers, both in adults and in children. All these drugs act as antimetabolite compounds, that is, they interfere with the ability of cancer cells to synthesize the nucleosides or the nucleotides necessary f...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.985648
更新日期:2015-05-01 00:00:00
abstract::Introduction: The target concentration strategy uses PKPD information for dose determination. Models have also quantified exposure-response relationships, improved understanding of developmental pharmacokinetics, rationalized dose prescription, provided insight into the importance of covariate information, explained d...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2020.1739648
更新日期:2020-04-01 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:INTRODUCTION:First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1401064
更新日期:2017-12-01 00:00:00
abstract:INTRODUCTION:Type 2 diabetes often involves derangements in lipid levels in addition to insulin resistance and diminishing insulin secretion. Colesevelam hydrochloride, a bile acid sequestrant (BAS), is approved for adjunctive therapy to diet and exercise for glycemic control in type 2 diabetes. In clinical studies in ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.672973
更新日期:2012-04-01 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:BACKGROUND:Testosterone replacement therapy in hypogonadal men has been used for > 60 years. The use of testosterone substitution is continuously growing and is given to aging men to improve the quality of life. Because testosterone use is associated with muscle strength enhancing effects, it has become a popular drug ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902976862
更新日期:2009-07-01 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:BACKGROUND:The number of patients eligible for cardiovascular therapies in general is forecast to increase substantially in the coming decades. However, the current list of potential future cardiovascular blockbuster drugs is alarmingly short. There is thus a clear need for innovative strategies to increase the efficie...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.6.665
更新日期:2008-06-01 00:00:00
abstract::Acetaminophen (APAP) hepatotoxicity is currently the single most important cause of acute liver failure in the US, and is associated with a significant number of deaths. The toxic response to APAP is triggered by a highly reactive metabolite N-acetyl-p-benzoquinone-imine. Following the hepatocellular initiation events...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.4.493
更新日期:2006-08-01 00:00:00
abstract:INTRODUCTION:Pemphigus is an autoimmune blistering disease of the skin and mucous membranes characterized by the development of autoantibodies against the desmosomal proteins, desmoglein-1 and -3. Before the advent of corticosteroids, therapy was almost fatal. The introduction of high-dose corticosteroid therapy has re...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.542149
更新日期:2011-02-01 00:00:00
abstract:INTRODUCTION:Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs that inhibit the pro-inflammatory effects of lipopolysaccharide (LPS) and improve outcome when added to conventional sepsis treatments are lacking. Eritoran tetrasodium (E5564) is a promising candidate t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.558190
更新日期:2011-04-01 00:00:00
abstract:INTRODUCTION:Mathematical models of dermal transport offer the advantages of being much faster and less expensive than in vitro or in vivo studies. The number of methods used to create such models has been increasing rapidly, probably due to the steady rise in computational power. Although each of the various approache...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1063615
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1041917
更新日期:2015-07-01 00:00:00
abstract:INTRODUCTION:Pregabalin is an alternative compound to SSRIs and SNRIs for the first-line treatment of generalized anxiety disorder (GAD). Areas covered: We describe the pharmacokinetic properties of pregabalin and their implications for the treatment of GAD. A search in the main database sources (Medline, ISI, Web of K...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1281247
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:Carboxylesterases (CEs) are ubiquitous enzymes responsible for the hydrolysis of numerous clinically useful drugs. As ester moieties are frequently included in molecules to improve their water solubility and bioavailability, de facto they become substrates for CEs. OBJECTIVE:In this review, we describe the ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.9.1153
更新日期:2008-09-01 00:00:00
abstract:INTRODUCTION:Therapeutic hypothermia is being employed clinically due to its neuro-protective benefits. Both critical illness and therapeutic hypothermia significantly affect drug disposition, potentially contributing to drug-therapy and drug-disease interactions. Currently, there is limited information on the known al...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.574127
更新日期:2011-07-01 00:00:00
abstract:INTRODUCTION:Type IV drug hypersensitivity remains an important clinical problem and an obstacle to the development of new drugs. Several forms of drug hypersensitivity are associated with expression of specific HLA alleles. Furthermore, drug-specific T-lymphocytes have been isolated from patients with reactions. Despi...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1441285
更新日期:2018-03-01 00:00:00
abstract:INTRODUCTION:Hemophilia A is a bleeding disorder resulting from a lack of clotting factor VIII (FVIII), and treatment typically consists of prophylactic replacement of the deficient factor. However, high between subject variability precludes the development of a 'one size fits all' dosing strategy and necessitates an i...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2016.1214711
更新日期:2016-11-01 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:BACKGROUND:Aerosol administration of therapeutics to the respiratory system represents a significant opportunity for many classes of drugs, both small molecules and macromolecules, including recently engineered peptide and protein therapeutics. However, minimally invasive assessment of drug absorption mechanisms in viv...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.4.333
更新日期:2008-04-01 00:00:00
abstract::Luminogenic cytochrome P450 (CYP) assays couple CYP enzyme activity to firefly luciferase luminescence in a technology called P450-Glo(TM) (Promega). Luminogenic substrates are used in assays of human CYP1A1, -1A2, -1B1, -2C8, -2C9, -2C19, -2D6, -2J2, -3A4, -3A7, -4A11, -4F3B, -4F12 and -19. The assays detect dose-dep...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.4.629
更新日期:2006-08-01 00:00:00
abstract::It has increasingly been recognized that few molecules move across the cell membrane without the assistance of transporter proteins. Large superfamilies of transporter proteins have been identified in every living cell, including microorganisms and mitochondria. This report reviews the role of transporters in physiolo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903176421
更新日期:2009-11-01 00:00:00
abstract:INTRODUCTION:Membrane transport proteins play a central role in regulating the disposition of endobiotics, dietary nutrients and environmental toxins. The inhibition of transporters by drugs has potential physiologic consequences. The full extent of the effect of drugs on the function of transporters is poorly understo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1372425
更新日期:2017-10-01 00:00:00
abstract:INTRODUCTION:The goal of pharmacologic therapy with antiepileptic drugs (AEDs) is to reduce the frequency of seizures and achieve a seizure-free state with minimal side effects. However 30% of patients treated with available AEDs continue to experience uncontrolled seizures. There is still need for new AEDs with enhanc...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1360278
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:The association between pregnancy and altered drug pharmacokinetic (PK) properties is acknowledged, as is its impact on drug plasma concentrations and thus therapeutic efficacy. However, there have been few robust PK studies of antimalarial use in pregnancy. Given that inadequate dosing for prevention or t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2020.1802425
更新日期:2020-09-01 00:00:00
abstract:INTRODUCTION:Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of T-cell neoplasms. Most patients with PTCL have a poor outcome with conventional therapies and are not cured without stem-cell transplantation. Pralatrexate, a novel antifolate chemotherapeutic agent, was rationally designed to impede folate m...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.595404
更新日期:2011-09-01 00:00:00
abstract:INTRODUCTION:Piperine has various pharmacological effects and can modulate the functional activity of metabolic enzymes and drug transporters. Consequently, there is a great interest in the application of piperine as an alternative medicine or bioavailability enhancer. Areas covered: This review deals with the effects ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1418854
更新日期:2018-01-01 00:00:00
abstract::Three first-line antituberculosis drugs, isoniazid, rifampicin and pyrazinamide, may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury ranges from a mild to severe form, and the associated mortality cases are not rare. The major drug-metabolizing enzyme of isoniazid is N-acetyl...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.3.1.1
更新日期:2007-02-01 00:00:00
abstract:INTRODUCTION:Adverse drug reactions with an immune pathogenesis are a problem in the clinic and an impediment to drug development. T lymphocytes are believed to play a role in the pathogenesis; however, the nature of the drug interaction with immune receptors remains an area of debate. AREAS COVERED:This article revie...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.992780
更新日期:2015-03-01 00:00:00