Related Experiment Video
Updated: Aug 29, 2025
Author Spotlight: Developing Novel Anticancer Therapeutics Targeting the DNA Damage Response
Published on: June 14, 2024
Targeting the DNA damage response in pediatric malignancies
Jenna M Gedminas1, Theodore W Laetsch1
1Department of Pediatrics, Children's Hospital of Philadelphia, Division of Oncology, Philadelphia, PA, USA.
Introduction:
High levels of DNA damage and mutations in DNA damage response genes create a high reliance on DNA damage repair in various tumors. This creates a vulnerability for new cancer therapies. Although there is extensive data for the use of these agents in adult tumors, the evaluation of these compounds in the pediatric population remains in the early stages.
Areas Covered:
In this review, we discuss the role of the DNA damage response as a therapeutic vulnerability in pediatric malignancies, provide a summary of clinical data for the use of DNA damage response inhibitors in cancer, and review how these compounds can be extended to the pediatric population.
Expert Opinion:
A number of pediatric cancers rely on robust DNA damage repair to maintain cell viability. This provides a therapeutic vulnerability in cancer cells resistant to other traditional therapies. Unfortunately, although clinical evaluation of inhibitors of various components of the DNA damage response has been done in adults, pediatric data remain limited. Further studies are needed to evaluate the efficacy of these compounds in the pediatric population.
Insights
Pediatric cancers with high DNA damage repair needs can be targeted by new therapies. DNA damage response inhibitors show promise, but more pediatric clinical data are needed.
Area of Science:
- Oncology
- Cancer Therapeutics
- Molecular Biology
Background:
- Tumors with high DNA damage exhibit reliance on DNA damage repair pathways.
- This reliance presents a vulnerability exploitable by targeted cancer therapies.
- Existing research on DNA damage response inhibitors is extensive in adult cancers but limited in pediatric malignancies.
Purpose of the Study:
- To review the role of DNA damage response as a therapeutic vulnerability in pediatric cancers.
- To summarize current clinical data on DNA damage response inhibitors in cancer treatment.
- To explore the potential application of these inhibitors in the pediatric population.
Main Methods:
- Literature review of DNA damage response pathways in cancer.
- Analysis of clinical trial data for DNA damage response inhibitors.
- Evaluation of existing studies concerning pediatric cancer treatment.
Main Results:
- Pediatric cancers often depend on DNA damage repair for survival.
- DNA damage response inhibitors represent a potential therapeutic strategy for resistant cancers.
- Limited clinical data exists for the efficacy of these inhibitors in pediatric patients.
Conclusions:
- DNA damage repair pathways are critical vulnerabilities in pediatric malignancies.
- Further clinical studies are essential to establish the safety and efficacy of DNA damage response inhibitors in children.
- Extending the use of these agents to pediatric populations requires dedicated research.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:37DNA Damage can Stall the Cell Cycle
02:56Treatment Resistant Cancers
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...
02:25Overview of DNA Repair
Chemically...
02:50Combination Therapies and Personalized Medicine
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...