Targeting DNA damage response and repair genes to enhance anticancer immunotherapy: rationale and clinical implication.
Giuseppe LambertiElisa AndriniMonia SisiAlessandro Di FedericoBiagio RicciutiPublished in: Future oncology (London, England) (2020)
DNA damage response and repair (DDR) 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 DDR 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.
Keyphrases
- dna damage
- dna damage response
- immune response
- dna repair
- papillary thyroid
- oxidative stress
- genome wide
- squamous cell
- induced apoptosis
- bioinformatics analysis
- dendritic cells
- toll like receptor
- lymph node metastasis
- young adults
- cell cycle arrest
- dna methylation
- genome wide analysis
- gene expression
- cell proliferation
- signaling pathway
- pi k akt