2021/11/17 by Mengting Chen, Renske Linstra, Marcel A.T.M. van Vugt
Biochemistry, Genetics and Molecular Biology · Medicine · #Cancer Immunotherapy and Biomarkers #Inflammasome and immune disorders #PARP inhibition in cancer therapy
paper · doi:10.1016/j.bbcan.2021.188661
openalex publication_date 2021/11/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
Genomic and chromosomal instability are hallmarks of cancer and shape the genomic composition of cancer cells, thereby determining their behavior and response to treatment. Various genetic and epigenetic alterations in cancer have been linked to genomic instability, including DNA repair defects, oncogene-induced replication stress, and spindle assembly checkpoint malfunction. A consequence of genomic and chromosomal instability is the leakage of DNA from the nucleus into the cytoplasm, either directly or through the formation and subsequent rupture of micronuclei. Cytoplasmic DNA subsequently activates cytoplasmic DNA sensors, triggering downstream pathways, including a type I interferon response. This inflammatory signaling has pleiotropic effects, including enhanced anti-tumor immunity and potentially results in sensitization of cancer cells to immune checkpoint inhibitors. However, cancers frequently evolve mechanisms to avoid immune clearance, including suppression of inflammatory signaling. In this review, we summarize inflammatory signaling pathways induced by various sources of genomic instability, adaptation mechanisms that suppress inflammatory signaling, and implications for cancer immunotherapy.