About this Research Topic
Drugs targeting DNA damage repair (DDR) are increasingly applied in anti-tumor therapies. DDR inhibition can induce and amplify DNA damage in cancer cells, with a deep impact on antitumor immune responses. Preclinical studies have shown that in addition to the direct poisonous effect on cancer cells, DDR-targeted drugs are also associated with increased tumor infiltrating lymphocytes, higher genomic instability, and higher tumor mutational burden (TMB) in cancer, enhancing the antitumor immune effect. This antitumor immune response can activate a long-lasting protective effect and help eliminate the residual cancer cells or maintain the metastases in a dormancy state. High quality studies on the mechanisms and translational research of immunological changes during DDR-targeted therapy will enable us to better understand the consequences of DDR-associated therapies in patients and ultimately benefit clinical practice.
This Research Topic aims at investigating the effects of DDR drugs on tumor immune microenvironment and immunogenic properties of tumor cells, in particular the molecular mechanisms that enhance antitumor immunity. For example, how DDR inhibitors can enhance the inflammatory IFN response to obtain a stronger anti-tumor effect, and the mechanisms underlying sustained anti-immune response caused by DDR-targeted drugs. Our ultimate goal is to support the development of combination therapies with DDR inhibitors and immune therapy to achieve stronger and more durable responses.
We welcome submissions of Original Research, Clinical Trial, Review, and Case Report on the following sub-themes:
• The relationship between DDR targeted therapies and patients’ response to immune checkpoint blockade (ICB) agents, as well as the immune-activating properties of DDR targeted therapies.
• Role of DNA repair defects (including DDR gene mutations, genomic instability and expression profile of DDR genes) in predicting immunotherapy response.
• The mechanisms of chemotherapy, radiation and DDR targeted therapy induced immunogenicity, including the cytosolic DNA sensing cGAS/STING-IFN pathway, neoantigen or tumor-associated antigen.
• The spatiotemporal and sequential treatment strategies for patients who are candidates for combination therapies with DDR inhibitors and immune therapy.
• Identification of novel DDR targets and combination strategies.
• Clinical update on the combination of DDR inhibitor and immunotherapy results and future perspectives.
Keywords: DNA damage response, oncoimmunology, DDR-targeting therapy, immunotherapy
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.