がん研セミナー（１２月９日）のお知らせ

演題：Topoisomerase-induced DNA damage and repair

演者：Drs. Yves Pommier(1) & Junko Murai(1,2)

(1)Developmental Therapeutics Branch and Laboratory of Molecular

Pharmacology, Center for Cancer Research, NCI, NIH, USA

(2)Laboratory for Malignancy Control Research, Medical Innovation

Center, Kyoto University Graduate School of Medicine

日時：2014年 12月9日（火）16:00-17:15

場所：吉田講堂

連絡先：清宮啓之 （内線5491）

抄録：　

Topoisomerases are ubiquitous enzymes, which are essential for cellular metabolism. They are the targets of some of the most active anticancer drugs as these drugs trap the enzyme-DNA cleavage complexes: irinotecan, topotecan, belotecan and indenoisoquinoline in clinical trials for Top1, and etoposide, doxorubicin and other anthracycline derivatives and mitoxantrone for Top2 (Pommier, Y. et al., 2012, Chem. Biol. 17: 421-33). Topoisomerase cleavage complexes can also be trapped by endogenous DNA lesions, which explains why cells have multiple pathways to repair these lesions, which can be inactivated as part of oncogenesis (Pommier, Y. et al. 2014 DNA Repair 19: 114-29). We will discuss recent insights on the pathways for the repair of topoisomerase-induced DNA damage and the novel therapeutic opportunities provided by the discovery of the repair enzyme, TDP1 and TDP2 (Tyrosyl-DNA-phosphodiesterases 1 and 2) (Pommier, Y. et al. 2014 DNA Repair 19: 114-29), the rationale combinations of Top1 inhibitors with PARP (polyADPriboses 1 and 2) (Murai, J. et al. 2014 J Pharmacol Exp Ther 349:408-16) or checkpoint inhibitors (ATR and Chk1) (Aris, S. and Pommier, Y. 2012 Cancer Res 72:979-89), and novel genomic determinants of response to Top1 inhibitors (Zoppoli, G. et al., 2012, Proc Natl Acad Sci USA 109:15030-5).

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