D-bait: A siDNA for regulation of DNA-protein kinases against DNA damage and its implications in cancer.

siDNA fragments, also called Dbait and Pbait, are small DNA oligonucleotides of 30-32 base pairs that cause impairment in DNA repair pathways. Like siRNA and miRNA molecules, which lead to the degradation of mRNA molecules through the Argonaute and Drosha machinery, respectively, Dbait molecules act as false DNA damage signals and trigger and exhaust the DNA repair machinery. In normal cells with no significant DNA damage, the influence of these molecules is negligible. However, in cancer, when there is heavy DNA damage due to replication and anticancer therapies, the cancer cell is heavily dependent on DNA repair proteins to keep the genome intact and limit breaks. This phenomenon primarily occurs during radiation therapy, as significant DNA damage surpasses several DNA repair mechanisms, causing an accumulation of unrepaired lesions and ultimately leading to cell death. This review explores the therapeutic capacity of siDNA molecules in cancer treatment by stimulating the repair mechanisms in cells that depend on DNA repair pathways. For aggressive malignancies such as glioblastoma, prostate cancer, and colorectal cancer, the use of siDNA as a radiosensitizer, especially when combined with other treatments, increases the vulnerability of tumor cells to radiation-induced DNA damage, hence potentially enhancing therapy results.