Pharmacogenetic Approach to Toxicity in Breast Cancer Patients Treated with Taxanes

Related Experiment Video

Updated: Mar 2, 2026

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
06:02

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers

Published on: February 20, 2017

8.0K

Silvia Angelini1,2, Andrea Botticelli1, Concetta Elisa Onesti3,2

  • 1Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.

Anticancer Research
|May 7, 2017
PubMed
Abstract

Insights

Single-nucleotide polymorphisms in ABCB1 may influence taxane chemotherapy toxicity in breast cancer patients. The ABCB1 3435 T/T genotype is associated with reduced toxicity, suggesting a potential biomarker for personalized treatment.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Taxanes are crucial in breast cancer chemotherapy.
  • Their metabolism involves cytochrome CYP3A and ABCB1 transporters.
  • Genetic variations (SNPs) in these genes may explain treatment toxicity differences.

Purpose of the Study:

  • To investigate the association between specific gene polymorphisms and taxane-induced toxicity in breast cancer patients.
  • To explore the role of CYP3A4, CYP3A5, and ABCB1 gene variants in treatment response.

Main Methods:

  • Retrospective analysis of 152 breast cancer patients undergoing taxane chemotherapy.
  • Genotyping performed for CYP3A4*1B, CYP3A5*3, and ABCB1 (C1236T, C3435T) polymorphisms.
  • Correlation analysis between genotypes and observed toxicities.

Main Results:

  • A statistically significant association was found between the ABCB1 3435 T/T genotype and lower-grade toxicities (p=0.05).
  • No significant associations were observed for CYP3A4*1B, CYP3A5*3, or the ABCB1 C1236T polymorphism.
  • The ABCB1 3435 T/T genotype appears linked to reduced taxane toxicity.

Conclusions:

  • The ABCB1 3435 T/T genotype may predict a lower incidence of toxicity in patients treated with taxanes.
  • Further large-scale prospective studies are warranted to confirm these findings.
  • This polymorphism could potentially guide personalized chemotherapy strategies.
Keywords:
ABCB1Breast cancerP-gpcytochrome P450polymorphismstaxanes

More Related Videos

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

14.1K
Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice08:41

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

Published on: October 27, 2014

24.0K

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...
56
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...
65
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...
83
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...
68
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...
53
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...
67