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001-es BibID:BIBFORM061387
Első szerző:Shen, Jianfeng
Cím:ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors / Jianfeng Shen, Yang Peng, Leizhen Wei, Wei Zhang, Lin Yang, Li Lan, Prabodh Kapoor, Zhenlin Ju, Qianxing Mo, Ie-Ming Shih, Ivan P. Uray, Xiangwei Wu, Powel H. Brown, Xuetong Shen, Gordon B. Mills, Guang Peng
Dátum:2015
Megjegyzések:ARID1A, SWI/SNF chromatin remodeling complex subunit, is a recently identified tumor suppressor that is mutated in a broad spectrum of human cancers. Thus, it is of fundamental clinical importance to understand its molecular functions and determine whether ARID1A deficiency can be exploited therapeutically. In this article, we report a key function of ARID1A in regulating the DNA damage checkpoint. ARID1A is recruited to DNA double-strand breaks (DSB) via its interaction with the upstream DNA damage checkpoint kinase ATR. At the molecular level, ARID1A facilitates efficient processing of DSB to single-strand ends and sustains DNA damage signaling. Importantly, ARID1A deficiency sensitizes cancer cells to PARP inhibitors in vitro and in vivo, providing a potential therapeutic strategy for patients with ARID1A-mutant tumors.SIGNIFICANCE:ARID1A has been identified as one of the most frequently mutated genes across human cancers. Our data suggest that clinical utility of PARP inhibitors might be extended beyond patients with BRCA mutations to a larger group of patients with ARID1A-mutant tumors, which may exhibit therapeutic vulnerability to PARP inhibitors.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Cancer Discovery. - 5 : 7 (2015), p. 752-767. -
További szerzők:Peng, Yang Wei, Leizhen Zhang, Wei Yang, Lin Lan, Li Kapoor, Prabodh Ju, Zhenlin Mo, Qianxing Shih, Ie-Ming Uray Iván Péter (1970-) (kutatóorvos) Wu, Xiangwei Brown, Powel H. Shen, Xuetong Mills, Gordon B. Peng, Guang
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