1文献来源SHAPIRO G I,LoRUSSO P,DOWLATI A,et al.A phase 1 study of RO6870810,a novel bromodomain and extra-terminal protein inhibitor,in patients with NUT carcinoma,other solid tumours,or diffuse large B-cell lymphoma[...1文献来源SHAPIRO G I,LoRUSSO P,DOWLATI A,et al.A phase 1 study of RO6870810,a novel bromodomain and extra-terminal protein inhibitor,in patients with NUT carcinoma,other solid tumours,or diffuse large B-cell lymphoma[J].Br J Cancer,2021,124(4):744−753.doi:10.1038/s41416-020-01180-1.2研究背景N端赖氨酸残基的组蛋白乙酰化是一种常见的翻译后修饰,在转录调控中起重要作用。被称为溴结构域(bromodomains,BRD)的蛋白质相互作用结构域能够识别并结合赖氨酸乙酰化基序,从而允许含BRD的蛋白质影响转录。BRD和超末端结构域(BRD and extra-terminal,BET)蛋白通过BRD模块中的疏水口袋与乙酰化染色质结合,随后募集并稳定调节转录效应因子。展开更多
1文献来源AMERATUNGA M,BRANA I,BONO P,et al.First-in-human phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours[J].Br J Cancer,2020,123(12):1730−1736.doi:10.1038/s41416-020-0107...1文献来源AMERATUNGA M,BRANA I,BONO P,et al.First-in-human phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours[J].Br J Cancer,2020,123(12):1730−1736.doi:10.1038/s41416-020-01077-z.2证据水平2a。3研究背景溴结构域和超末端结构域(bromodomain and extra-terminal,BET)家族(BRD2、BRD3、BRD4和BRDT)包含两个串联的异染色质蛋白域,这些域可结合乙酰化赖氨酸残基,促进转录蛋白招募到染色质上。BRD4定位于染色质的启动子和增强子区域,并通过与中介复合体和pTEFb的相互作用来调节RNA聚合酶Ⅱ介导的延伸和转录。展开更多
1文献来源LEWIN J,SORIA J C,STATHIS A,et al.PhaseⅠb trial with birabresib,a small-molecule inhibitor of bromodomain and extraterminal proteins,in patients with selected advanced solid tumors[J].J Clin Oncol,2018,36(30...1文献来源LEWIN J,SORIA J C,STATHIS A,et al.PhaseⅠb trial with birabresib,a small-molecule inhibitor of bromodomain and extraterminal proteins,in patients with selected advanced solid tumors[J].J Clin Oncol,2018,36(30):3007−3014.doi:10.1200/JCO.2018.78.2292.2证据水平1b。3研究背景伴睾丸核蛋白(nuclear protein in testis,NUT)基因重排的中线癌又称NUT癌,是一种罕见的具有高度侵袭性的鳞状癌。它的发病与位于15号染色体长臂的NUT中线癌家族成员1基因(NUT midline carcinoma family member 1,NUTM1)重排有关。展开更多
Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great pote...Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great potential for melanoma treatment.展开更多
文摘1文献来源SHAPIRO G I,LoRUSSO P,DOWLATI A,et al.A phase 1 study of RO6870810,a novel bromodomain and extra-terminal protein inhibitor,in patients with NUT carcinoma,other solid tumours,or diffuse large B-cell lymphoma[J].Br J Cancer,2021,124(4):744−753.doi:10.1038/s41416-020-01180-1.2研究背景N端赖氨酸残基的组蛋白乙酰化是一种常见的翻译后修饰,在转录调控中起重要作用。被称为溴结构域(bromodomains,BRD)的蛋白质相互作用结构域能够识别并结合赖氨酸乙酰化基序,从而允许含BRD的蛋白质影响转录。BRD和超末端结构域(BRD and extra-terminal,BET)蛋白通过BRD模块中的疏水口袋与乙酰化染色质结合,随后募集并稳定调节转录效应因子。
文摘1文献来源AMERATUNGA M,BRANA I,BONO P,et al.First-in-human phase 1 open label study of the BET inhibitor ODM-207 in patients with selected solid tumours[J].Br J Cancer,2020,123(12):1730−1736.doi:10.1038/s41416-020-01077-z.2证据水平2a。3研究背景溴结构域和超末端结构域(bromodomain and extra-terminal,BET)家族(BRD2、BRD3、BRD4和BRDT)包含两个串联的异染色质蛋白域,这些域可结合乙酰化赖氨酸残基,促进转录蛋白招募到染色质上。BRD4定位于染色质的启动子和增强子区域,并通过与中介复合体和pTEFb的相互作用来调节RNA聚合酶Ⅱ介导的延伸和转录。
文摘1文献来源LEWIN J,SORIA J C,STATHIS A,et al.PhaseⅠb trial with birabresib,a small-molecule inhibitor of bromodomain and extraterminal proteins,in patients with selected advanced solid tumors[J].J Clin Oncol,2018,36(30):3007−3014.doi:10.1200/JCO.2018.78.2292.2证据水平1b。3研究背景伴睾丸核蛋白(nuclear protein in testis,NUT)基因重排的中线癌又称NUT癌,是一种罕见的具有高度侵袭性的鳞状癌。它的发病与位于15号染色体长臂的NUT中线癌家族成员1基因(NUT midline carcinoma family member 1,NUTM1)重排有关。
基金This work was supported by grants from the National Natural Science Foundation of China(82103183,82102803,82272849)the Natural Science Foundation of Hunan Province(2022JJ40767,2021JJ40976)+1 种基金the Natural Science Fund for Outstanding Youths in Hunan Province(2023JJ20093)the National Key Research and Development Program(2022YFC2504700).
文摘Dear Editor,Ferroptosis,an iron-dependent form of cell death driven by overwhelming lipid peroxidation,represents a vulnerability in cancers,and therapeutic strategies to further potentiate ferroptosis hold great potential for melanoma treatment.
