Related Experiment Video

Updated: Jun 9, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

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

Published on: December 7, 2014

Interaction of tyrosine kinase inhibitors with the MDR- related ABC transporter proteins

Xiao-Kun Wang1, Li-Wu Fu

  • 1State Key Laboratory of Oncology in Southern China, Cancer center, Sun Yat-sen University, Guangzhou, 510060, China.

Current Drug Metabolism
|September 4, 2010
PubMed

Insights

Tyrosine kinase inhibitors (TKIs) show promise in cancer treatment but can be hindered by ATP binding cassette (ABC) transporters. Some TKIs may reverse drug resistance, while others can cause it.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Tyrosine kinase inhibitors (TKIs) are targeted anticancer agents that penetrate cell membranes.
  • Overexpression of ATP binding cassette (ABC) transporters can lead to tumor cell resistance to TKIs.
  • Some TKIs may increase ABC transporter expression, reducing their efficacy.

Purpose of the Study:

  • To review the interactions between TKIs and MDR-related ABC transporters.
  • To discuss the clinical implications of these interactions for cancer therapy.

Main Methods:

  • Literature review of TKIs in clinical use or trials.
  • Analysis of TKI interactions with ABCB1, ABCC1, and ABCG2 transporters.
  • Discussion of TKI-ABC transporter interplay in multidrug resistance (MDR).

Main Results:

  • TKIs exhibit varied interactions with ABC transporters.
  • Some TKIs are substrates for ABC transporters, leading to reduced efficacy.
  • Other TKIs can inhibit ABC transporters, potentially reversing MDR.

Conclusions:

  • Understanding TKI-ABC transporter interactions is crucial for optimizing cancer therapy.
  • Strategies to overcome TKI resistance mediated by ABC transporters are needed.
  • Further research into TKIs that modulate ABC transporters may yield new therapeutic approaches.

More Related Videos

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Related Concept Videos

ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
ABC Transporters: Importer01:27

ABC Transporters: Importer

ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
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 specific...
Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
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...