Abstract
Background: Methotrexate (MTX) is a folate analogue with high therapeutic efficiency in the treatment of cancers and autoimmune diseases. The efficacy and toxicity of MTX may be altered by genetic polymorphisms in genes involved in MTX metabolic pathway. Personalized pharmacotherapy based on gene polymorphisms enables a more efficient, compatible and cost-effective treatment of patients.
Objective: The present article aims to review genetic polymorphisms associated with MTX pharmacokinetics, toxicity, and outcome, and points out future development directions of individualized MTX therapy.
Methods: Details regarding the pharmacogenetics and pharmacogenomics of MTX are obtained from PubMed literatures.
Conclusion: The influences of single nucleotide polymorphisms (SNPs) in genes involved in MTX pathway are controversial. Many pharmacogenetic associations are disease specific and race specific. Present studies have almost limited to some certain ethnic groups and diseases. The data from these studies are not convincing enough to draw far-reaching conclusions about the applicability of MTX pharmacogenetics in clinical practice. Studies with large scale and multiple centers are needed in the future. MTX-PG inhibits folic metabolism through three mechanisms. TS, MTHFR and ATIC are the rate-limiting enzymes separately. The function of SNPs in these genes is often onesided. Works focusing on the analysis of polymorphism in MTX transporters should be more efficient and meaningful.
Keywords: MTX, SNP, efficacy, toxicity, pharmacogenomics, polymorphisms.
Graphical Abstract
Call for Papers in Thematic Issues
Impact of brain tissue binding and plasma protein binding of drugs in DMPK
The impression of brain tissue binding (BTB) or plasma protein binding (PPB) in Drug Metabolism and Pharmacokinetics is critical to understanding the distribution, efficacy, and potential toxicity of drugs that target the central nervous system (CNS). BTB and high PPB influence the distribution of drugs in the body and their ...read more
Interaction between drugs and endocrine diseases
The introduction of highly active antiretroviral therapy accelerated studies and our understanding on the interaction between pharmacological therapies and endocrine diseases. Drugs can precipitate endocrine via different mechanisms, including direct alteration of hormone production and secretion, dysregulation of hormonal axis, effects on hormonal transport, receptor-binding, and cellular signalling. Common drug-induced ...read more
Metabolism-Mediated Xenobiotic Toxicity
Considering the potent modulation of biotransformation enzyme expression and activities by various therapeutic drugs and environmental chemicals, and the commonly combined exposure of humans to both drugs and the ever increasing environmental pollutants simultaneously, knowledge about the combined toxic effects by modulating biotransformation enzymes, such as P450s, UDP- glucuronosyltransferases, and ...read more
Safety evaluation of vaccine combination
Vaccine combination safety evaluation is a critical field within immunology and public health that focuses on assessing the safety and efficacy of combining different vaccines to maximize protection against various diseases while minimizing potential adverse effects. This process is significant because it ensures that vaccines can be administered together without ...read more
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Current Drug Therapy
Related Books
Andrographolide and its Analogs: Botanical Sources, Phytochemistry, Pharmacology, and Biotechnology
Novel Drug Delivery Systems (Part 2)
AI Innovations in Drug Delivery and Pharmaceutical Sciences; Advancing Therapy through Technology
Anthocyanins: Pharmacology and Nutraceutical Importance
Computer-Aided Drug Discovery Methods: A Brief Introduction
The Roles and Responsibilities of Clinical Pharmacists in Hospital Settings
Bioactive Compounds from Medicinal Plants for Cancer Therapy and Chemoprevention
Nanotechnology in Drug Discovery
Drug Addiction Mechanisms in the Brain
Software and Programming Tools in Pharmaceutical Research
104
8