DNA damage response (DDR) is an intricate and interconnected network consisting of signaling pathways, enzymes, factors, and molecules to sense and transduce DNA damage and to activate DNA repair pathways to repair DNA lesions or induce programmed cell death. DDR and repair pathways play a key role in maintaining the cellular genome integrity and stability and is also extensively involved in the regulation of cell cycle and DNA replication, as well as the transformation of cell malignance.

Errors in DDR and DNA repair pathways are associated with almost all types of cancer, which could lead to sustained cell proliferation, enhanced invasive and metastatic capabilities, angiogenesis, and chemo-/radio-resistance and are now considered a key characteristic of both solid and liquid tumors. For example, mutations in BRCA1, BRCA2, and PALB2 genes result in defective homologous recombination repair and are associated with the carcinogenesis of breast and ovarian cancer; dysfunction in DNA mismatch repair genes is involved in genomic instability and predisposes individuals to colon and uterine tumors. Defects in DDR and repair pathways can also be seen in lung cancer, hepatocellular cancer, esophageal cancer, and leukemia. The genetic and pathological changes in DDR and repair pathways give us the chance for the diagnosis and prognostic evaluation of cancer.

DDR has several distinct components, specifically signaling pathway proteins such as poly (ADP-ribose) polymerase (PARP), ATM and Rad3 related (ATR), DNA dependent protein kinases (DNA-PKs), checkpoint kinase-1 (CHK1), and other potential targets. In fact, targeting of these DDR pathways has become a therapeutic strategy for a variety of malignancies. On the other hand, the generation and expression of tumor-associated self-antigens due to reduced DNA repair pathways and elevated mutational burden could help the development of immunotherapy against these tumors.

We invite researchers to submit research articles, review articles, and clinical studies on the topic highlighted to this special issue, addressing various issues and insights into DNA repair in cancer.

Potential topics include but are not limited to the following:

• DNA damage response in cancer biology and therapy
• Regulation of DNA repair in carcinogenesis
• Role of DNA damage and repair in pathological changes in cancer
• Diagnosis and treatment options targeting defects in DNA repair in cancer