Related Experiment Video

Updated: May 12, 2026

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

Targeting ATR in DNA damage response and cancer therapeutics

Emmanouil Fokas1, Remko Prevo, Ester M Hammond

  • 1Gray Institute for Radiation Oncology and Biology, Department of Oncology, Oxford University, Oxford, United Kingdom; Department of Radiation Therapy and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.

Cancer Treatment Reviews
|April 16, 2013
PubMed

Insights

Targeting the ATR pathway, crucial for genome stability, can selectively kill cancer cells by increasing replication stress. New inhibitors show promise for enhancing cancer treatments like radiation and chemotherapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • The Ataxia Telangiectasia and Rad3-related (ATR) protein is vital for maintaining genome integrity.
  • ATR regulates DNA replication and the DNA damage response (DDR) pathway.
  • Preclinical studies indicate ATR inhibition can enhance cancer cell killing.

Purpose of the Study:

  • To review the function of ATR in DNA replication and DDR.
  • To explore the potential of ATR inhibition in cancer therapy.
  • To discuss recent advancements in selective ATR inhibitors.

Main Methods:

  • Literature review of ATR function and DDR.
  • Analysis of preclinical data on ATR inhibition in cancer models.
  • Examination of studies on ATR inhibitors in vitro and in vivo.

Main Results:

  • ATR inhibition exacerbates replication stress in oncogene-driven tumors, promoting cell death.
  • ATR blockade sensitizes tumor cells to radiation and chemotherapy.
  • ATR inhibition selectively sensitizes cancer cells, not normal cells, to DNA damage.
  • Hypoxic conditions enhance ATR blockade-induced cell death via replication stress.

Conclusions:

  • ATR inhibition is a promising strategy for cancer treatment, particularly in combination therapies.
  • Recent identification of selective ATR inhibitors facilitates further research and clinical development.
  • Targeting ATR offers a potential approach to selectively sensitize cancer cells to DNA-damaging agents.
Keywords:
ATRCancerChemotherapyDNA damageRadiationReplication stressTherapeutics

More Related Videos

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells05:18

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Published on: June 9, 2020

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage10:59

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

Related Concept Videos

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...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...