Chemosensitivity of IDH1-Mutated Gliomas Due to an Impairment in PARP1-Mediated DNA Repair

被引：167

作者：

Lu, Yanxin ^{[1
]}

Kwintkiewicz, Jakub ^{[2
,3
]}

Liu, Yang ^{[1
]}

Tech, Katherine ^{[4
]}

Frady, Lauren N. ^{[2
,3
]}

Su, Yu-Ting ^{[1
]}

Bautista, Wendy ^{[1
]}

Moon, Seog In ^{[1
]}

MacDonald, Jeffrey ^{[4
]}

Ewend, Matthew G. ^{[2
,3
]}

Gilbert, Mark R. ^{[1
]}

Yang, Chunzhang ^{[1
]}

Wu, Jing ^{[1
,2
,3
]}

机构：

[1] NCI, Neurooncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA

[2] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[3] Univ North Carolina Chapel Hill, Dept Neurosurg, Chapel Hill, NC USA

[4] Univ North Carolina Chapel Hill, Sch Med, Dept Biomed Engn, Chapel Hill, NC USA

来源：

CANCER RESEARCH | 2017年 / 77卷 / 07期

关键词：

MUTANT IDH1; ISOCITRATE DEHYDROGENASE; OLIGODENDROGLIAL TUMORS; ADJUVANT TEMOZOLOMIDE; GLIOBLASTOMA CELLS; PHASE-III; MUTATIONS; CANCER; INHIBITOR; SURVIVAL;

D O I：

10.1158/0008-5472.CAN-16-2773

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Mutations in isocitrate dehydrogenase (IDH) are the most prevalent genetic abnormalities in lower grade gliomas. The presence of these mutations in glioma is prognostic for better clinical outcomes with longer patient survival. In the present study, we found that defects in oxidative metabolism and 2-HG production confer chemosensitization in IDH1-mutated glioma cells. In addition, temozolomide (TMZ) treatment induced greater DNA damage and apoptotic changes in mutant glioma cells. The PARP1-associated DNA repair pathway was extensively compromised in mutant cells due to decreased NAD_ availability. Targeting the PARP DNA repair pathway extensively sensitized IDH1-mutated glioma cells to TMZ. Our findings demonstrate a novel molecular mechanism that defines chemosensitivity in IDH-mutated gliomas. Targeting PARP-associated DNA repair may represent a novel therapeutic strategy for gliomas.

引用

页码：1709 / 1718

页数：10

共 50 条

[41] Surgically treated incidentally discovered low-grade gliomas are mostly IDH mutated and 1p19q co-deleted with favorable prognosis
Zhang, Zhen-Yu
Chan, Aden Ka-Yin
Ng, Ho-Keung
Ding, Xiao-Jie
Li, Yan-Xi
Shi, Zhi-Feng
Zhu, Wei
Zhong, Ping
Wang, Yin
Mao, Ying
Yao, Yu
Zhou, Liang-Fu
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY, 2014, 7 (12): : 8627 - U917
[42] IDH1-mutated Crohn's disease-associated small bowel adenocarcinomas: Distinctive pathological features and association with MGMT methylation and serrated-type dysplasia
Guerini, Camilla
Furlan, Daniela
Ferrario, Giuseppina
Grillo, Federica
Libera, Laura
Arpa, Giovanni
Klersy, Catherine
Lenti, Marco, V
Riboni, Roberta
Solcia, Enrico
Fassan, Matteo
Mastracci, Luca
Ardizzone, Sandro
Moens, Annick
De Hertogh, Gert
Ferrante, Marc
Graham, Rondell P.
Sessa, Fausto
Paulli, Marco
Di Sabatino, Antonio
Vanoli, Alessandro
HISTOPATHOLOGY, 2024, 84 (03) : 515 - 524
[43] A PARP1-BRG1-SIRT1 axis promotes HR repair by reducing nucleosome density at DNA damage sites
Chen, Yu
Zhang, Haiping
Xu, Zhu
Tang, Huanyin
Geng, Anke
Cai, Bailian
Su, Tao
Shi, Jiejun
Jiang, Cizhong
Tian, Xiao
Seluanov, Andrei
Huang, Jun
Wan, Xiaoping
Jiang, Ying
Gorbunova, Vera
Mao, Zhiyong
NUCLEIC ACIDS RESEARCH, 2019, 47 (16) : 8563 - 8580
[44] Evaluation of a DNA demethylating agent in combination with all-trans retinoic acid for IDH1-mutant gliomas
Rosa, Marina da Costa
Yamashita, Alex Shimura
Riggins, Gregory J.
NEURO-ONCOLOGY, 2022, 24 (05) : 711 - 723
[45] The PARP1 Inhibitor Niraparib Represses DNA Damage Repair and Synergizes with Temozolomide for Antimyeloma Effects
Shen, Hong-Yuan
Tang, Hai-Long
Zheng, Yan-Hua
Feng, Juan
Dong, Bao-Xia
Chen, Xie-Qun
JOURNAL OF ONCOLOGY, 2022, 2022
[46] Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2
Inoue, Satoshi
Li, Wanda Y.
Tseng, Alan
Beerman, Isabel
Elia, Andrew J.
Bendall, Sean C.
Lemonnier, Francois
Kron, Ken J.
Cescon, David W.
Hao, Zhenyue
Lind, Evan F.
Takayama, Naoya
Planello, Aline C.
Shen, Shu Yi
Shih, Alan H.
Larsen, Dana M.
Li, Qinxi
Snow, Bryan E.
Wakeham, Andrew
Haight, Jillian
Gorrini, Chiara
Bassi, Christian
Thu, Kelsie L.
Murakami, Kiichi
Elford, Alisha R.
Ueda, Takeshi
Straley, Kimberly
Yen, Katharine E.
Melino, Gerry
Cimmino, Luisa
Aifantis, Iannis
Levine, Ross L.
De Carvalho, Daniel D.
Lupien, Mathieu
Rossi, Derrick J.
Nolan, Garry P.
Cairns, Rob A.
Mak, Tak W.
CANCER CELL, 2016, 30 (02) : 337 - 348
[47] Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair
Dow, Jonathan
Krysztofiak, Adam
Liu, Yanfeng
Colon-Rios, Daniel A.
Rogers, Faye A.
Glazer, Peter M.
MOLECULAR CANCER RESEARCH, 2021, 19 (12) : 2057 - 2067
[48] Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1
Calvo, Jennifer A.
Moroski-Erkul, Catherine A.
Lake, Annabelle
Eichinger, Lindsey W.
Shah, Dharini
Jhun, Iny
Limsirichai, Prajit
Bronson, Roderick T.
Christiani, David C.
Meira, Lisiane B.
Samson, Leona D.
PLOS GENETICS, 2013, 9 (04):
[49] Chromosome 17p Homodisomy Is Associated With Better Outcome in 1p19q Non-Codeleted and IDH-Mutated Gliomas
Labussiere, Marianne
Rahimian, Amithys
Giry, Marine
Boisselier, Blandine
Schmitt, Yohann
Polivka, Marc
Mokhtari, Karima
Delattre, Jean-Yves
Idbaih, Ahmed
Labreche, Karim
Alentorn, Agusti
Sanson, Marc
ONCOLOGIST, 2016, 21 (09) : 1131 - 1135
[50] DNA Repair Enzyme Poly(ADP-Ribose) Polymerase 1/2 (PARP1/2)-Targeted Nuclear Imaging and Radiotherapy
Nguyen, Nghia T.
Pacelli, Anna
Nader, Michael
Kossatz, Susanne
CANCERS, 2022, 14 (05)

← 1 2 3 4 5 →