Related Experiment Video
Updated: May 12, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
DNA repair dysregulation from cancer driver to therapeutic target
1Newcastle University, Northern Institute for Cancer Research, Newcastle upon Tyne NE2 4HH, UK. nicola.curtin@ncl.ac.uk
Abstract:
Dysregulation of DNA damage repair and signalling to cell cycle checkpoints, known as the DNA damage response (DDR), is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. Dysfunction of one DNA repair pathway may be compensated for by the function of another compensatory DDR pathway, which may be increased and contribute to resistance to DNA-damaging chemotherapy and radiotherapy. Therefore, DDR pathways make an ideal target for therapeutic intervention; first, to prevent or reverse therapy resistance; and second, using a synthetic lethal approach to specifically kill cancer cells that are dependent on a compensatory DNA repair pathway for survival in the context of cancer-associated oxidative and replicative stress. These hypotheses are currently being tested in the laboratory and are being translated into clinical studies.
Insights
Dysregulation of the DNA damage response (DDR) impacts cancer predisposition and treatment. Targeting DDR pathways offers strategies to overcome therapy resistance and selectively eliminate cancer cells.
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- The DNA damage response (DDR) is crucial for maintaining genomic stability.
- Dysregulation of DDR pathways is linked to cancer development and influences treatment efficacy.
- Compensatory DDR pathways can lead to resistance against DNA-damaging therapies.
Purpose of the Study:
- To investigate the therapeutic potential of targeting DDR pathways in cancer.
- To explore strategies for overcoming chemoresistance and radioresistance.
- To develop synthetic lethal approaches for cancer treatment.
Main Methods:
- Laboratory research on DDR pathway function and dysregulation.
- Translational studies moving from bench to clinical trials.
- Investigating compensatory mechanisms in DNA repair.
Main Results:
- DDR pathway dysregulation is a hallmark of cancer.
- Compensatory DDR pathways can confer resistance to chemotherapy and radiotherapy.
- Targeting DDR presents a dual therapeutic strategy.
Conclusions:
- DDR pathways are promising targets for cancer therapy.
- Interventions can potentially reverse or prevent therapy resistance.
- Synthetic lethality offers a targeted approach to kill cancer cells dependent on compensatory DDR.
More Related Videos
06:44Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
Published on: April 28, 2021
09:29Analysis of Nonhomologous End Joining and Homologous Recombination Efficiency in HEK-293T Cells Using GFP-Based Reporter Systems
Published on: February 2, 2024
Related Concept Videos
01:08Nucleotide Excision Repair
02:25Overview of DNA Repair
Chemically...
01:08Nucleotide Excision Repair
02:36DNA Damage can Stall the Cell Cycle
02:25Overview of DNA Repair
Chemically...
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...