Tuyển tập các báo cáo nghiên cứu khoa học ngành y học tạp chí Medical Sciences dành cho các bạn sinh viên ngành y tham khảo đề tài: PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers? | Int. J. Med. Sci. 2006 3 117 Review International Journal of Medical Sciences ISSN 1449-1907 2006 3 4 117-123 2006 Ivyspring International Publisher. All rights reserved PARP-1 inhibitors are they the long-sought genetically specific drugs for BRCA1 2-associated breast cancers Joseph A. De Soto and Chu-Xia Deng Genetics of Development and Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health 10 9N105 10 Center Drive Bethesda MD 20892 USA. Correspondence to Dr. Chu-Xia Deng Phone 301 402-7225 Fax 301 480-1135. Email chuxiad@ Received Accepted Published Recent studies demonstrated that PARP-1 poly ADP-ribose polymerase-1 inhibitors kill breast cancer associated gene-1 and -2 BRCA1 2 deficient cells with extremely high efficiency while BRCA - and BRCA cells are relatively non-responsive to the treatment. It was therefore proposed that PARP-1 inhibitors might be the long-sought genetically specific drugs that are both safe and effective for treating BRCA1 2-associated breast cancers. However a report published in a recent issue of the International Journal of Biological Sciences revealed that PARP-1 inhibitors although able to kill naive BRCA1 mutant cells with high specificity both in vitro and in vivo exhibit minimal specificity in inhibiting the growth of mouse mammary tumor cells irrespective of their BRCA1 status in allograft nude mice. Non-specific inhibition in human BRCA1 BRCA1 - and BRCA1- - breast cancer cells by PARP-1 inhibitors was also observed. Additional mutations occurring during cancer progression may be a culprit although the exact cause for the resistance of BRCA1- -breast cancer cells to PARP-1 inhibitors remains elusive. These findings suggest that PARP inhibition may serve as an approach for the prevention of BRCA related breast cancer and may be useful in combination with other chemotherapeutic agents in the treatment of .
