Related Experiment Video

Updated: Apr 22, 2026

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

1.6K

Asparagine synthetase polymorphisms and toxicity and efficacy of asparaginases

Vassilios I Avramis1

  • 1Keck School of Medicine, University of Southern California, Los Angeles, California. Children's Hospital Los Angeles, Los Angeles, California. vavramis@chla.usc.edu.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 9, 2014
PubMed

Insights

Asparaginase treatments for leukemia show optimal outcomes with moderate toxicity. Genetic variations in asparagine synthetase may predict severe side effects in some patients, warranting further clinical evaluation.

Area of Science:

  • Biochemistry
  • Oncology
  • Pharmacogenomics

Background:

  • Asparaginase enzymes create "tumor starvation" environments for leukemia treatment.
  • Drug administration is frequently limited by dose-limiting toxicities.
  • Patient outcomes correlate with moderate toxicity levels.

Purpose of the Study:

  • To investigate the role of asparagine synthetase polymorphisms in predicting severe toxicities.
  • To evaluate clinical correlations between genetic variations and patient responses to asparaginase therapy.

Main Methods:

  • Analysis of asparagine synthetase gene polymorphisms.
  • Correlation of genetic data with observed patient toxicities and treatment outcomes.

Main Results:

  • Specific asparagine synthetase polymorphisms are associated with severe host toxicities in certain patient subsets.
  • Other polymorphisms do not appear to confer increased toxicity risk.
  • Moderate toxicity levels correlate with optimal treatment outcomes.

Conclusions:

  • Asparagine synthetase polymorphisms are potential predictive biomarkers for asparaginase toxicity.
  • Personalized treatment strategies based on genetic profiles may mitigate severe adverse events.
  • Further clinical studies are needed to validate these findings.

More Related Videos

LERLIC-MS/MS for In-depth Characterization and Quantification of Glutamine and Asparagine Deamidation in Shotgun Proteomics08:01

LERLIC-MS/MS for In-depth Characterization and Quantification of Glutamine and Asparagine Deamidation in Shotgun Proteomics

Published on: April 9, 2017

7.7K
Caenorhabditis elegans as a Model System for Discovering Bioactive Compounds Against Polyglutamine-Mediated Neurotoxicity08:16

Caenorhabditis elegans as a Model System for Discovering Bioactive Compounds Against Polyglutamine-Mediated Neurotoxicity

Published on: September 21, 2021

4.5K

Related Concept Videos

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
93
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
80
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
155
Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
219
Drug toxicity: Drug–Drug Interaction01:30

Drug toxicity: Drug–Drug Interaction

Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
407
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
184