Alterations of DNA damage response pathway: Biomarker and therapeutic strategy for cancer immunotherapy

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Genomic instability is a hallmark of cancer, driving malignant transformation.
• Alterations in DNA damage response (DDR) pathways are central to genomic instability.
• DDR alterations influence the tumor microenvironment, including neoantigen generation and PD-L1 expression.

Purpose of the Study:

• To review the fundamental knowledge of DDR pathways.
• To elucidate mechanisms by which DDR alterations induce genomic instability.
• To explore the impact of DDR alterations on the immune system and their potential in cancer immunotherapy.

Main Methods:

• Literature review of DNA damage response pathways.
• Analysis of mechanisms linking DDR alterations to genomic instability.
• Examination of the interplay between DDR, neoantigen production, PD-L1 expression, and cGAS-STING signaling.
• Review of current and potential applications in cancer immunotherapy.

Main Results:

• DDR pathway alterations are a primary driver of genomic instability in cancer.
• Altered DDR pathways modulate immune responses through neoantigen generation and PD-L1 upregulation.
• Interactions with signaling pathways like cGAS-STING are influenced by DDR status.
• DDR alterations present potential as biomarkers and therapeutic targets in cancer immunotherapy.

Conclusions:

• DDR alterations are critical mediators of cancer development and progression.
• Targeting DDR pathways offers promising strategies for enhancing cancer immunotherapy efficacy.
• Further research into DDR alterations can identify novel biomarkers and therapeutic targets for personalized cancer treatment.