Related Experiment Video

Updated: Jun 8, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

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

Published on: September 19, 2018

Moving towards dose individualization of tyrosine kinase inhibitors

Heinz-Josef Klümpen1, Caroline F Samer, Ron H J Mathijssen

  • 1Department of Medical Oncology, Academic Medical Center, University of Amsterdam, 1100DD Amsterdam, The Netherlands. h.klumpen@amc.uva.nl

Cancer Treatment Reviews
|September 14, 2010
PubMed

Insights

Molecular targeted therapies like tyrosine kinase inhibitors (TKIs) show variable patient responses. Individualizing TKI doses based on pharmacokinetics and biomarkers could improve cancer treatment efficacy and reduce toxicity.

Area of Science:

  • Oncology
  • Pharmacology
  • Biomarkers

Background:

  • Molecular targeted therapies, particularly tyrosine kinase inhibitors (TKIs), represent a significant advance in cancer treatment.
  • Current practice predominantly uses fixed dosing for TKIs, potentially leading to suboptimal outcomes due to high inter-individual variability in pharmacokinetics (PK).

Purpose of the Study:

  • To review the pharmacokinetics, toxicity, and efficacy of ten common TKIs.
  • To explore strategies for optimizing TKI prescription and dose individualization.

Main Methods:

  • Systematic review of pharmacokinetic, toxicity, and efficacy data for ten commonly used TKIs.
  • Analysis of associations between toxicity, efficacy, and potential biomarkers.

Main Results:

  • Significant interpatient variability in TKI pharmacokinetics was confirmed.
  • Certain toxicities (e.g., skin rash with erlotinib) may serve as efficacy surrogate markers.
  • Biomarkers for dose individualization and alternative dosing strategies (TDM, genotype/phenotype, toxicity-adjusted) were identified.

Conclusions:

  • Fixed dosing of TKIs may not be optimal due to PK variability.
  • Dose individualization using therapeutic drug monitoring, biomarkers, or toxicity-guided approaches holds promise for personalized cancer therapy.
  • Prospective studies are required to validate these personalized dosing strategies and develop dosing algorithms.

More Related Videos

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia10:49

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

Published on: September 18, 2013

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

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...
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...
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...
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...
Dosage Regimen: Individualization01:24

Dosage Regimen: Individualization

Individualization in dosing regimens is the customization of medication doses for individual patients. Its necessity arises from the goal of maximizing therapeutic benefits while minimizing risks. This approach is pivotal because human responses to drugs can vary widely; what is effective for one person may be inadequate or excessive for another. Interpatient (intersubject) variability refers to differences in drug responses between individuals, while intrapatient (intrasubject) variability...
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...