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Published on: April 28, 2021
Nucleic Acid Sensing Pathways in DNA Repair Targeted Cancer Therapy
Bingteng Xie1,2, Aiqin Luo1,2
1School of Life Science, Beijing Institute of Technology, Beijing, China.
Abstract:
The repair of DNA damage is a complex process, which helps to maintain genome fidelity, and the ability of cancer cells to repair therapeutically DNA damage induced by clinical treatments will affect the therapeutic efficacy. In the past decade, great success has been achieved by targeting the DNA repair network in tumors. Recent studies suggest that DNA damage impacts cellular innate and adaptive immune responses through nucleic acid-sensing pathways, which play essential roles in the efficacy of DNA repair targeted therapy. In this review, we summarize the current understanding of the molecular mechanism of innate immune response triggered by DNA damage through nucleic acid-sensing pathways, including DNA sensing via the cyclic GMP-AMP synthase (cGAS), Toll-like receptor 9 (TLR9), absent in melanoma 2 (AIM2), DNA-dependent protein kinase (DNA-PK), and Mre11-Rad50-Nbs1 complex (MRN) complex, and RNA sensing via the TLR3/7/8 and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). Furthermore, we will focus on the recent developments in the impacts of nucleic acid-sensing pathways on the DNA damage response (DDR). Elucidating the DDR-immune response interplay will be critical to harness immunomodulatory effects to improve the efficacy of antitumor immunity therapeutic strategies and build future therapeutic approaches.
Insights
DNA damage repair in cancer cells affects treatment efficacy. Emerging research shows DNA damage triggers immune responses via nucleic acid sensing, influencing therapy outcomes and offering new cancer treatment strategies.
Area of Science:
- Molecular Biology
- Immunology
- Oncology
Background:
- DNA damage repair is crucial for genome stability and cancer treatment efficacy.
- Cancer cells' ability to repair DNA damage impacts therapeutic outcomes.
- Recent findings link DNA damage to innate and adaptive immune responses via nucleic acid sensing.
Purpose of the Study:
- To review the molecular mechanisms of innate immune responses to DNA damage through nucleic acid-sensing pathways.
- To summarize the impact of nucleic acid-sensing pathways on the DNA damage response (DDR).
- To highlight the interplay between DDR and immune responses for improved cancer therapies.
Main Methods:
- Literature review focusing on DNA damage, nucleic acid sensing, and immune response pathways.
- Analysis of DNA sensing mechanisms (cGAS, TLR9, AIM2, DNA-PK, MRN).
- Examination of RNA sensing mechanisms (TLR3/7/8, RIG-I-like receptors).
Main Results:
- DNA damage activates innate immunity through various DNA and RNA sensing pathways.
- These pathways modulate the DNA damage response (DDR).
- The interplay between DDR and immune signaling is critical for therapeutic efficacy.
Conclusions:
- Understanding the DDR-immune response crosstalk is essential for developing novel cancer therapies.
- Targeting nucleic acid-sensing pathways can enhance antitumor immunity.
- Harnessing immunomodulatory effects holds promise for improving cancer treatment strategies.
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