The DNA Damage Response and Infl ammation in Cancer

Genomic stability in normal cells is crucial to avoid oncogenesis. Accordingly, multiple components of the DNA damage response (DDR) operate as bona fide tumor suppressor proteins by preserving genomic stability, eliciting the demise of cells with unrepairable DNA lesions, and engaging cell-extrinsic oncosuppression via immunosurveillance. That said, DDR signaling can also favor tumor progression and resistance to therapy. Indeed, DDR signaling in cancer cells has been consistently linked to the inhibition of tumor-targeting immune responses. Here, we discuss the complex interactions between the DDR and infl ammation in the context of oncogenesis, tumor progression, and response to therapy.Signifi cance: Accumulating preclinical and clinical evidence indicates that DDR is intimately connected to the emission of immunomodulatory signals by normal and malignant cells, as part of a cell-extrinsic program to preserve organismal homeostasis. DDR-driven inflammation, however, can have diametrically opposed effects on tumor-targeting immunity. Understanding the links between the DDR and inflammation in normal and malignant cells may unlock novel immunotherapeutic paradigms to treat cancer.

Automated summary

Genomic stability is vital for normal cells to prevent oncogenesis. The DNA damage response (DDR) plays a role as a tumor suppressor protein in preserving genomic stability, inducing the death of cells with unrepairable DNA lesions and engaging cell-extrinsic oncosuppression through immunosurveillance. However, DDR signaling in cancer cells can inhibit tumor-targeting immune responses, favoring tumor progression and therapy resistance. This article discusses the complex interactions between DDR and inflammation in the context of oncogenesis, tumor progression, and response to therapy.