DNA damage cancer

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Poly(ADP-ribose) polymerase (PARP) plays an important role in a number of cellular processes, including DNA repair. Elevated PARP has been observed in some cancer patients, and combination of PARP inhibitors with cytotoxic agents has demonstrated S3mergistic effects in preclinical models. Thus, PARP inhibitors in combination with conventional DNA-damaging cancer treatments may offer a new approach to various cancers. AG-14699 [26] is the lead in a series of inhibitors of PARP and is being evaluated in phase II studies for the potential treatment of cancer including melanoma, breast cancer, and ovarian cancer. 

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Wu, X., Takenaka, K., Sonoda, E., Hochegger, H., Kawanishi, S., Kawamoto, T., Takeda, S., and Yamazoe, M. (2006). Critical roles for polymerase t, in cellular tolerance to nitric oxide-induced DNA damage. Cancer Res. 66, 748-754. 

Though DNA damage-based therapies havebeen in use for many years, it has remained unclear why such treatment often causes the selective death of tumor cells while sparing adjacent normal tissue. The genetic alterations that occur in cancers that alter the DNA damage reponse may explain why such therapy can be efficacious. 

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Roy, D, Floyd, R.A. and Liehr, J.G. (1991). Elevated 8-hydroxy-deoxy anosine levels in DNA of diethylstilbcstrol-treated Syrian hamsters covalent DNA damage by free radicals generated by redox cycling of diethyl-stilbestrol. Cancer Res. 51, 3882-3885. 

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