Related Experiment Video

Updated: Jan 9, 2026

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.5K

Do genetic polymorphisms influence imatinib trough concentrations in patients with chronic myeloid leukemia? A

Francisco Cezar Aquino de Moraes1, Gustavo Tadeu Freitas Uchôa Matheus2, Luis Henrique Rios Moreira Rego3

  • 1Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.

Expert Review of Anticancer Therapy
|December 10, 2025
PubMed
Abstract

Insights

Genetic variations in ABCB1 and ABCG2 significantly impact imatinib therapy for chronic myeloid leukemia (CML). Pharmacogenetic screening can optimize treatment efficacy and safety by identifying patients likely to have altered imatinib plasma concentrations.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Chronic myeloid leukemia (CML) treatment relies on tyrosine kinase inhibitors like imatinib, but patient responses vary.
  • Genetic polymorphisms in drug transporter genes ABCB1 and ABCG2 are known to influence imatinib plasma trough concentrations (Ctrough).

Purpose of the Study:

  • To conduct a meta-analysis evaluating the association between ABCB1 and ABCG2 genetic polymorphisms and imatinib Ctrough in CML patients.
  • To assess the clinical implications of these genetic variations for imatinib therapy optimization.

Main Methods:

  • A meta-analysis was performed on nine studies involving 1,098 heterozygous patients, 519 variant carriers, and 896 wild-type individuals.
  • Statistical analyses utilized fixed-effect models, with heterogeneity assessed using the I² statistic.

Main Results:

  • Significantly higher imatinib Ctrough was observed in patients with specific ABCB1 genotypes (c.3435C>T TT, c.2677G>T GT, and TT) compared to wild-type.
  • Carriers of the ABCG2 c.412C>A CA genotype also showed increased Ctrough compared to CC genotype.

Conclusions:

  • The findings highlight the significant role of ABCB1 and ABCG2 genetic polymorphisms in determining imatinib plasma concentrations.
  • Pharmacogenetic screening is supported as a strategy to personalize imatinib therapy, enhance treatment efficacy, and mitigate adverse outcomes in CML patients.
Keywords:
ABCB1ABCG2Chronic myeloid leukemiaimatinibmeta-analysis

More Related Videos

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.2K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.6K

Related Concept Videos

Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.8K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.6K
Therapeutic Drug Monitoring: Affecting Factors01:29

Therapeutic Drug Monitoring: Affecting Factors

Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
175
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
192
Nonlinear Pharmacokinetics: Role of Transporters01:27

Nonlinear Pharmacokinetics: Role of Transporters

A drug's nonlinear kinetics can be influenced by a diverse range of transporter proteins that serve as crucial players in drug distribution. These transporters, found within cells, can enhance or reduce local drug concentrations by facilitating the influx or efflux of drugs. For instance, the expression of xenobiotic transporters can be influenced by factors such as age and gender, potentially impacting the linearity of drug response.
Polymorphisms occurring in drug transporters can alter...
255
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
236