Related Experiment Video

Updated: Jun 7, 2026

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
08:12

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer

Published on: March 14, 2019

Pharmacogenetic interaction analysis for the efficacy of systemic treatment in metastatic colorectal cancer

J Pander1, J A M Wessels1, H Gelderblom2

  • 1Department of Clinical Pharmacy & Toxicology.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|November 5, 2010
PubMed
Abstract

Insights

Genetic markers in TYMS and VEGF predict treatment response in metastatic colorectal cancer (mCRC). This interaction profile improves prediction of progression-free survival (PFS) for capecitabine, oxaliplatin, and bevacizumab therapy.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Pharmacogenetic markers can optimize patient selection for metastatic colorectal cancer (mCRC) treatment.
  • Genetic interaction analysis is crucial for understanding polygenic contributions to drug response.

Purpose of the Study:

  • To identify genetic interaction profiles predicting treatment efficacy in mCRC patients.
  • To evaluate the association of specific polymorphisms with progression-free survival (PFS).

Main Methods:

  • Analyzed 17 polymorphisms in 279 previously untreated mCRC patients receiving capecitabine, oxaliplatin, and bevacizumab (CAPOX-B).
  • Employed multifactor dimensionality reduction analysis to identify genetic interaction profiles for PFS.

Main Results:

  • A genetic interaction profile involving the TYMS enhancer region and VEGF +405G>C polymorphism significantly predicted PFS.
  • Patients with the beneficial profile had a median PFS of 13.3 months versus 9.7 months for the unfavorable profile (HR 1.58).
  • No single polymorphism was individually associated with PFS.

Conclusions:

  • A genetic interaction between TYMS enhancer region and VEGF +405G>C polymorphisms predicts CAPOX-B efficacy in mCRC patients.
  • This genetic profile serves as a valuable predictor for treatment outcomes in mCRC.

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

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

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...
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...
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,...