Related Experiment Video

Updated: Jun 4, 2026

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
10:26

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

Published on: November 7, 2019

Integrating pharmacogenetics into gemcitabine dosing--time for a change?

Joseph Ciccolini1, Cédric Mercier, Laetitia Dahan

  • 1Pôle Oncologie, La Timone University Hospital of Marseille, 267 Rue St Pierre, 13385 Marseille, France.

Nature Reviews. Clinical Oncology
|February 10, 2011
PubMed

Insights

Identifying biomarkers for gemcitabine therapy is crucial for improving anticancer drug efficacy and reducing toxic effects. Pharmacogenetic testing, focusing on enzymes like cytidine deaminase, can personalize treatment and enhance patient care.

Area of Science:

  • Oncology
  • Pharmacology
  • Biomarker Discovery

Background:

  • Gemcitabine is a key anticancer agent with a narrow therapeutic index, often causing adverse effects due to abnormal pharmacokinetics.
  • Predicting patient response and toxicity is critical for optimizing gemcitabine treatment in clinical oncology.
  • Tumor-level molecular determinants are often used as biomarkers, but drug disposition factors are also important.

Approach:

  • Investigate genetic and functional deregulations affecting gemcitabine disposition.
  • Focus on the role of cytidine deaminase, the primary enzyme in gemcitabine detoxification.
  • Validate biomarkers for pharmacogenetic testing to guide gemcitabine administration.

Key Points:

  • Abnormal pharmacokinetics of gemcitabine significantly contribute to its toxicity and treatment failure.
  • Cytidine deaminase deregulation is a potential cause of adverse effects and reduced efficacy.
  • Biomarkers predicting gemcitabine response and toxicity are needed for personalized medicine.

Conclusions:

  • Identifying and validating biomarkers for gemcitabine pharmacogenetics is essential for improving patient outcomes.
  • Pharmacogenetic testing can help tailor gemcitabine therapy, minimizing adverse events and maximizing efficacy.
  • This approach represents a significant step towards personalized cancer treatment.

More Related Videos

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform06:21

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

Published on: May 10, 2024

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice08:57

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice

Published on: October 5, 2017

Related Concept Videos

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 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 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...
Pharmacogenetics and Pharmacogenomics: Overview01:29

Pharmacogenetics and Pharmacogenomics: Overview

Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
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,...
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...