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Related Concept Videos

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...
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...
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...
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...
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...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...

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Updated: Jun 11, 2026

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
06:21

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Published on: May 10, 2024

Irinotecan pharmacogenomics.

Sharon Marsh1, Janelle M Hoskins

  • 1UNC Institute for Pharmacogenomics & Individualized Therapy, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. smarsh@pharmacy.ualberta.ca

Pharmacogenomics
|July 7, 2010
PubMed
Summary
This summary is machine-generated.

Genetic variations in UGT1A1, ABCC2, TDP1, and XRCC1 influence irinotecan toxicity and response. Understanding these genetic factors can help personalize cancer treatment and manage severe side effects.

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Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Irinotecan, a camptothecin analog, is a vital anticancer drug.
  • Severe toxicities, sometimes life-threatening, are associated with irinotecan treatment.
  • Genetic factors are increasingly recognized for their role in drug response and toxicity.

Purpose of the Study:

  • To explore the genetic underpinnings of irinotecan toxicity and response.
  • To highlight the role of specific genes in irinotecan pharmacokinetics and pharmacodynamics.
  • To provide insights for personalized irinotecan therapy.

Main Methods:

  • Review of existing literature on irinotecan pharmacogenomics.
  • Analysis of studies investigating gene polymorphisms and their association with irinotecan outcomes.
  • Focus on key genes including UGT1A1, ABCC2, TDP1, and XRCC1.

Main Results:

  • UGT1A1 promoter polymorphism (UGT1A1*28) is strongly linked to irinotecan toxicity, with a dose-dependent relationship.
  • ABCC2 gene variations contribute significantly to irinotecan-related toxicities.
  • Pharmacodynamic genes TDP1 and XRCC1 also play a role in both irinotecan toxicity and treatment efficacy.

Conclusions:

  • Genetic variations, particularly in UGT1A1, ABCC2, TDP1, and XRCC1, are critical determinants of irinotecan toxicity and response.
  • Pharmacogenomic profiling can aid in predicting and managing irinotecan-induced adverse events.
  • Personalized medicine approaches incorporating genetic information may optimize irinotecan therapy outcomes.