Targeting DNA Damage Response and Immune Checkpoint for Anticancer Therapy

Deficiency in DNA damage response (DDR) genes leads to impaired DNA repair functions that will induce genomic instability and facilitate cancer development. However, alterations of DDR genes can serve as biomarkers for the selection of suitable patients to receive specific therapeutics, such as immu...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-03, Vol.23 (6), p.3238
Main Authors: Huang, Jau-Ling, Chang, Yu-Tzu, Hong, Zhen-Yang, Lin, Chang-Shen
Format: Article
Language:English
Subjects:
Angiogenesis
Apoptosis
Ataxia
Biomarkers
Breast
Breast cancer
Cancer immunotherapy
Cancer therapies
Cell cycle
cGAS-STING
Chemotherapy
clinical trial
Clinical trials
Colorectal cancer
Deoxyribonucleic acid
DNA
DNA Damage
DNA damage response
DNA methylation
DNA Repair
Gene expression
Genes
Genomic instability
Growth factors
Humans
Immune checkpoint
Immune response
Immune system
Immunity
Immunotherapy
Inflammation
Interferon
Kinases
Leukemia
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
Pancreatic cancer
PARP
Patients
Polymerization
Proteins
Review
RNA polymerase
Therapeutic targets
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Summary:Deficiency in DNA damage response (DDR) genes leads to impaired DNA repair functions that will induce genomic instability and facilitate cancer development. However, alterations of DDR genes can serve as biomarkers for the selection of suitable patients to receive specific therapeutics, such as immune checkpoint blockade (ICB) therapy. In addition, certain altered DDR genes can be ideal therapeutic targets through adapting the mechanism of synthetic lethality. Recent studies indicate that targeting DDR can improve cancer immunotherapy by modulating the immune response mediated by cGAS-STING-interferon signaling. Investigations of the interplay of DDR-targeting and ICB therapies provide more effective treatment options for cancer patients. This review introduces the mechanisms of DDR and discusses their crucial roles in cancer therapy based on the concepts of synthetic lethality and ICB. The contemporary clinical trials of DDR-targeting and ICB therapies in breast, colorectal, and pancreatic cancers are included.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23063238