Targeting DNA damage response and repair genes to enhance anticancer immunotherapy: rationale and clinical implication

DNA damage response and repair ( ) genes play a central role in the life of actively replicating cells, cooperating to maintenance of genomic integrity. However, exogenous or endogenous factors, including deficiency in genes, can cause different degrees of DNA damage that profoundly impacts the tumo...

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Bibliographic Details
Published in:Future oncology (London, England) England), 2020-08, Vol.16 (23), p.1751-1766
Main Authors: Lamberti, Giuseppe, Andrini, Elisa, Sisi, Monia, Federico, Alessandro Di, Ricciuti, Biagio
Format: Article
Language:English
Subjects:
Apoptosis
Biomarkers
Cancer therapies
Cell cycle
Chemotherapy
Clinical outcomes
Deoxyribonucleic acid
DNA
DNA damage
DNA damage and repair
DNA methylation
DNA repair
Enzymes
immune checkpoint inhibitors
Immune system
Immunotherapy
Kinases
Metastasis
Mutation
mutational burden
PARP inhibitor
PD-L1
Proteins
STING
Tumors
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Summary:DNA damage response and repair ( ) genes play a central role in the life of actively replicating cells, cooperating to maintenance of genomic integrity. However, exogenous or endogenous factors, including deficiency in genes, can cause different degrees of DNA damage that profoundly impacts the tumor immunogenicity and enhance antitumor immune response through neoantigen-dependent and neoantigen-independent mechanisms. Inhibition of DDRs is already an effective therapeutic strategy in different cancer types. In addition, because DDR inhibition can also induce and amplify DNA damage in cancer cells, with a deep impact on antitumor immune responses, combining DDR inhibitors with immune checkpoint inhibitors represent an attractive therapeutic strategy to potentially improve the clinical outcomes of patients with metastatic cancer. In this review, we provide an overview of the rational and potential of combining DDR and immune checkpoint inhibition to exploit the enhanced antitumor immune response induced by DNA damage.
ISSN:1479-6694
1744-8301
DOI:10.2217/fon-2020-0215