Emerging cancer therapeutic opportunities target DNA-repair systems

PKB/Akt promotes DSB repair in cancer cells through upregulating Mre11 expression following ionizing radiation

“…Mre11, one of important DSB repair elements, is required for DNA-DSB repair including non-homologous end-joining repair system and homologous recombination repair system. Ding et al, 2006;Williams et al, 2007Williams et al, , 2008. It also can stabilize Rad50 and Nbs1 polypeptides and act as a chaperone for the MRN complex (Takemura et al, 2006).…”

“…Researchers have focused on DNArepair interference as an adjuvant approach for combating intrinsic or acquired tumor radioresistance (Ding et al, 2006). Therefore, it is very important to examine the molecules that regulate DNA-repair pathways.…”

“…DNA double-strand breaks (DSBs) are the most important DNA lesions leading to cancer cell death following exposure to ionizing radiation (IR) (Khanna and Jackson, 2001). However, an elevated DNA-repair capacity in tumor cells lead to radiation resistance and severely limits the efficacy of IR, and the balance between DNA damage and repair determines the final therapeutic consequences (Ding et al, 2006).…”

Chimeric adenoviral vector Ad5/F35-mediated APE1 siRNA enhances sensitivity of human colorectal cancer cells to radiotherapy in vitro and in vivo

“…DNA repair proteins are becoming important targets for enhancing cancer therapy. [4][5][6] In particular, APE1 is becoming a leading target due to its central involvement in DNA repair signaling. 31 The BER pathway is essential for the removal of DNA bases damaged by alkylation or oxidation.…”

“…A new and emerging concept designed to sensitize cancer cells to DNA-damaging agents, that is chemotherapy, and/or radiation is inhibition of various proteins in the DNA repair pathways. [4][5][6] The human apurinic/apyrimidinic endonuclease (APE1) is an essential enzyme in the base excision repair (BER) pathway, which is responsible for the repair of oxidative and alkylation DNA damage. APE1 accounts for nearly all of the abasic site cleavage activity in most cultured human cell lines, [7][8][9][10] and is essential for the protection of cells against the toxic effects of several classes of DNA-damaging agents.…”