Targeting DNA damage response to enhance cancer immunotherapy efficacy: molecular mechanisms and clinical advances

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• The DNA damage response (DDR) is crucial for genomic stability.
• Targeting DDR pathways offers therapeutic advances but faces resistance and toxicity.
• Cancer immunotherapy shows efficacy but has modest response rates and immunosuppression issues.

Purpose of the Study:

• To review DDR-targeted cancer therapies and their mechanisms for enhancing tumor immunogenicity.
• To explore clinical advances in combining DDR inhibitors with immunotherapy.
• To provide insights for optimizing combination strategies.

Main Methods:

• Systematic review of DDR-targeted cancer therapies.
• Analysis of molecular mechanisms for enhancing tumor immunogenicity.
• Review of clinical studies on DDR inhibitor and immunotherapy combinations.

Main Results:

• DDR inhibitors can potentiate antitumor immunity through increased neoantigen release and cGAS-STING pathway activation.
• Combinations of DDR inhibitors with immune checkpoint inhibitors show synergistic promise.
• Early development of DDR inhibitors with novel immunotherapeutic approaches is underway.

Conclusions:

• Combining DDR inhibitors with immunotherapy is a promising strategy to overcome limitations of single-agent therapies.
• Understanding the molecular mechanisms is key to optimizing these combination strategies.
• Further research and clinical trials are needed to translate these findings into effective cancer treatments.