Related Experiment Video

Updated: Jan 23, 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

15.2K

Axitinib overcomes multiple imatinib resistant cKIT mutations including the gatekeeper mutation T670I in

Feiyang Liu1, Fengming Zou1, Cheng Chen2

  • 1High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, P. R. China Precision Medicine Research Laboratory of Anhui Province, Hefei, Anhui, P. R. China.

Therapeutic Advances in Medical Oncology
|June 18, 2019
PubMed
Abstract

Insights

Axitinib shows potent activity against various KIT mutations in gastrointestinal stromal tumors (GISTs), including those resistant to current therapies. This suggests axitinib as a potential new treatment option for GIST patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Gastrointestinal stromal tumors (GISTs) are driven by KIT kinase mutations.
  • Approved therapies like imatinib face limitations due to acquired resistance mutations in KIT.
  • Novel therapeutic strategies are needed to overcome treatment resistance in GIST.

Purpose of the Study:

  • To investigate the KIT inhibitory activity of axitinib in preclinical GIST models.
  • To evaluate axitinib's efficacy against primary and secondary KIT mutations.
  • To assess axitinib's potential as a treatment for GIST patients resistant to existing therapies.

Main Methods:

  • Assessed axitinib activity against wild-type and mutant KIT using protein-based assays.
  • Utilized engineered and GIST-derived cell lines to evaluate drug response.
  • Analyzed axitinib binding modes to KIT and its mutants.
  • Tested axitinib in GIST patient-derived primary cells and preclinical models.

Main Results:

  • Axitinib demonstrated potent inhibition of various primary and secondary KIT mutations.
  • Axitinib showed superior activity against certain KIT mutations compared to imatinib, sunitinib, and regorafenib.
  • Axitinib effectively inhibited imatinib-resistant KIT mutants (T670I, V654A) in vitro and in vivo.

Conclusions:

  • Axitinib exhibits significant anti-tumor activity in preclinical GIST models.
  • Results support the potential use of axitinib for GIST patients unresponsive or intolerant to current treatments.
  • Axitinib represents a promising therapeutic candidate for overcoming resistance in GIST.
Keywords:
GISTsaxitinibcKITcKIT T670Idrug resistance

More Related Videos

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

25.0K
Author Spotlight: Modeling Brain Tumors In Vivo Using Electroporation-Based Delivery of Plasmid DNA Representing Patient Mutation Signatures04:01

Author Spotlight: Modeling Brain Tumors In Vivo Using Electroporation-Based Delivery of Plasmid DNA Representing Patient Mutation Signatures

Published on: June 23, 2023

3.0K

Related Concept Videos

Mutations01:39

Mutations

Overview
94.4K
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.1K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
39.8K
Mutation, Gene Flow, and Genetic Drift01:09

Mutation, Gene Flow, and Genetic Drift

In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
63.3K
Mutations in Microorganisms01:18

Mutations in Microorganisms

Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
568
Point and Frameshift Mutations01:30

Point and Frameshift Mutations

Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
926