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Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
Targeting DNA repair proteins: a promising avenue for cancer gene therapy
Jean-Philippe Belzile1, Sibgat A Choudhury, Denis Cournoyer
1Department of Oncology, Division of Radiation Oncology, McGill University Health Center, Montreal, Quebec, Canada.
Abstract:
Enhanced DNA repair in many cancer cells can be correlated to the resistance to cancer treatment, and thus contributes to a poor prognosis. Ionizing radiation and many anti-cancer drugs induce DNA double-strand breaks (DSBs), which are usually regarded as the most toxic types of DNA damages. Repair of DNA DSBs is vital for maintaining genomic stability and hence crucial for survival and propagation of all cellular organisms. Therefore, reducing the capacity of cancer cells to repair DSBs could sensitize tumors to radio/chemotherapy. Many investigators have used gene therapy strategies to down-regulate or inactivate proteins involved in the repair of DSBs in order to reduce the survival of cancer cells. Herein, are reviewed several protein candidates that have been targeted by different gene therapy approaches. Results obtained from in vitro and in vivo experiments are presented and discussed in the perspective of potential gene therapy clinical trials.
Insights
Targeting DNA repair mechanisms in cancer cells could improve treatment efficacy. Inhibiting DNA double-strand break (DSB) repair proteins via gene therapy may sensitize tumors to radio/chemotherapy, offering new clinical trial avenues.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Enhanced DNA repair in cancer cells correlates with treatment resistance and poor prognosis.
- DNA double-strand breaks (DSBs) are highly toxic DNA lesions induced by radio/chemotherapy.
- Efficient repair of DSBs is critical for cancer cell survival and genomic stability.
Purpose of the Study:
- To review gene therapy strategies targeting proteins involved in DSB repair.
- To explore the potential of reducing cancer cell DSB repair capacity to enhance treatment sensitivity.
- To discuss the clinical applicability of targeting DSB repair pathways.
Main Methods:
- Review of existing literature on gene therapy approaches for DSB repair inhibition.
- Analysis of in vitro and in vivo experimental results from studies targeting DSB repair proteins.
- Discussion of protein candidates and gene therapy strategies employed.
Main Results:
- Several protein candidates involved in DSB repair have been targeted by gene therapy.
- In vitro and in vivo studies demonstrate the potential of these strategies.
- Targeting DSB repair can reduce cancer cell survival and sensitize tumors to therapy.
Conclusions:
- Down-regulating or inactivating DSB repair proteins via gene therapy is a promising strategy.
- This approach holds potential for sensitizing tumors to radio/chemotherapy.
- Further research and clinical trials are warranted to translate these findings.
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