BET inhibition as a new strategy for the treatment of gastric cancer.
BET inhibition as a new strategy for the treatment of gastric cancer.
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DOI：
10.18632/oncotarget.9766
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发表时间：
2016-07-12
期刊：
影响因子：
--
通讯作者：
Müller S
中科院分区：
文献类型：
--
作者：
Montenegro RC;Clark PG;Howarth A;Wan X;Ceroni A;Siejka P;Nunez-Alonso GA;Monteiro O;Rogers C;Gamble V;Burbano R;Brennan PE;Tallant C;Ebner D;Fedorov O;O'Neill E;Knapp S;Dixon D;Müller S
胃癌是世界范围内最常见的恶性肿瘤之一，也是癌症死亡的主要原因。胃癌的预后通常很差，因为这种癌症对常用的化疗不是很敏感。表观遗传修饰在胃癌中起着关键作用，并有助于这种恶性肿瘤的发生和发展。为了在该目标领域探索新的治疗选择，我们筛选了针对胃癌细胞系的表观遗传抑制剂库，并鉴定了BET家族溴结构域的抑制剂作为胃癌细胞增殖的有效抑制剂。在这里，我们表明，泛BET抑制剂（+）-JQ 1以及新开发的特异性异恶唑抑制剂PNZ 5都显示出对胃癌细胞生长的有效抑制。有趣的是，我们发现与来自亚洲患者的胃癌细胞相比，来自巴西患者的胃癌细胞的抗增殖反应存在差异，后者在很大程度上对BET抑制具有抗性。随着BET抑制剂进入临床试验，这些发现为未来针对胃癌的治疗提供了第一个起点。
Gastric cancer is one of the most common malignancies and a leading cause of cancer death worldwide. The prognosis of stomach cancer is generally poor as this cancer is not very sensitive to commonly used chemotherapies. Epigenetic modifications play a key role in gastric cancer and contribute to the development and progression of this malignancy. In order to explore new treatment options in this target area we have screened a library of epigenetic inhibitors against gastric cancer cell lines and identified inhibitors for the BET family of bromodomains as potent inhibitors of gastric cancer cell proliferations. Here we show that both the pan-BET inhibitor (+)-JQ1 as well as a newly developed specific isoxazole inhibitor, PNZ5, showed potent inhibition of gastric cancer cell growth. Intriguingly, we found differences in the antiproliferative response between gastric cancer cells tested derived from Brazilian patients as compared to those from Asian patients, the latter being largely resistant to BET inhibition. As BET inhibitors are entering clinical trials these findings provide the first starting point for future therapies targeting gastric cancer.
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影响因子：
24.5
作者：
Deng N;Goh LK;Wang H;Das K;Tao J;Tan IB;Zhang S;Lee M;Wu J;Lim KH;Lei Z;Goh G;Lim QY;Tan AL;Sin Poh DY;Riahi S;Bell S;Shi MM;Linnartz R;Zhu F;Yeoh KG;Toh HC;Yong WP;Cheong HC;Rha SY;Boussioutas A;Grabsch H;Rozen S;Tan P
通讯作者：
Tan P
DOI：
10.1107/s090744491003982x
发表时间：
2011-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Evans PR
通讯作者：
Evans PR
影响因子：
4.6
作者：
Baker EK;Taylor S;Gupte A;Sharp PP;Walia M;Walsh NC;Zannettino AC;Chalk AM;Burns CJ;Walkley CR
通讯作者：
Walkley CR
选择性抑制BET溴结构域。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K