Related Experiment Video

Updated: Aug 7, 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

Fusion tyrosine kinases: a result and cause of genomic instability

E T P Penserga1, T Skorski

  • 1Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA 19140, USA. tskorski@temple.edu

Oncogene
|June 21, 2006
PubMed

Insights

Fusion tyrosine kinases (FTKs) arise from DNA damage and promote cancer by driving uncontrolled cell growth and resisting treatment. These fusion proteins also worsen DNA damage, leading to disease progression and drug resistance.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Reciprocal chromosomal translocations can result from unrepaired DNA double-strand breaks, often caused by environmental factors or cellular stress.
  • These translocations frequently target tyrosine kinase genes, leading to the formation of fusion tyrosine kinases (FTKs).

Purpose of the Study:

  • To elucidate the mechanisms by which fusion tyrosine kinases (FTKs) contribute to cancer development and treatment resistance.
  • To understand the multifaceted roles of FTKs in cellular processes, including DNA repair, cell cycle regulation, and apoptosis.

Main Methods:

  • The study likely involved analyzing genetic alterations in cancer cells, focusing on chromosomal translocations.
  • Investigating the functional consequences of FTK expression on cell proliferation, apoptosis, DNA repair, and response to therapies.
  • Examining the impact of FTKs on cellular signaling pathways and the generation of reactive oxygen species.

Main Results:

  • FTKs exhibit constitutive kinase activity, driving deregulated cell proliferation, apoptosis, differentiation, and adhesion.
  • FTKs enhance DNA repair, prolong cell cycle checkpoints (G2/M and S phases), and increase Bcl-X(L) expression, promoting resistance to antitumor treatments.
  • FTKs can stimulate reactive oxygen species production and increase spontaneous DNA damage in tumor cells.
  • FTKs impair DNA repair fidelity, leading to further genetic abnormalities, imatinib resistance, and malignant progression.

Conclusions:

  • Fusion tyrosine kinases are key oncogenic drivers with pleiotropic effects that promote cancer initiation, progression, and therapeutic resistance.
  • The compromised DNA repair fidelity induced by FTKs contributes significantly to the accumulation of genetic instability and adverse clinical outcomes.
  • Targeting FTKs and understanding their complex roles are crucial for developing effective cancer therapies.

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

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...