Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells.
Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells.
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DOI：
10.1371/journal.pone.0279522
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Hosseini, Arshad
中科院分区：
文献类型：
--
作者：
Choupani, Edris;Madjd, Zahra;Saraygord-Afshari, Neda;Kiani, Jafar;Hosseini, Arshad
三阴性乳腺癌（TNBC）是一种侵袭性亚型乳腺癌（BC），目前缺乏特定的治疗方案。因此，化疗仍然是主要的治疗方法，开发新的靶点是临床的首要焦点。雄激素受体（AR）已成为TNBC亚型的治疗靶点，在各种临床研究中显示出实质性的临床益处。大量研究表明，癌症与细胞周期机制组成部分的变化有关。虽然细胞周期蛋白依赖性激酶（CDK） 4/6抑制剂在治疗er阳性BC中是成功的，但它们对TNBC患者的治疗没有帮助。我们研究了在AR阳性TNBC细胞系中，CDK4/6抑制剂（ribociclib）与AR抑制剂（enzalutamide）联合使用的可能性。Ribociclib对TNBC细胞有抑制作用。此外，我们发现enzalutamide降低了ar阳性细胞的细胞迁移/侵袭、克隆生成能力、细胞周期进程和细胞生长。恩杂鲁胺治疗可增加ribociclib对AR+ TNBC细胞的细胞抑制作用。此外，与单独治疗相比，AR和CDK4/6的双重抑制在AR+ TNBC模型中显示出协同作用。
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) that currently lacks specific therapy options. Thus, chemotherapy continues to be the primary treatment, and developing novel targets is a top clinical focus. The androgen receptor (AR) has emerged as a therapeutic target in a subtype of TNBC, with substantial clinical benefits shown in various clinical studies. Numerous studies have shown that cancer is associated with changes in components of the cell cycle machinery. Although cell cycle cyclin-dependent kinase (CDK) 4/6 inhibitors are successful in the treatment of ER-positive BC, they are not helpful in the treatment of patients with TNBC. We investigated the possibility of combining CDK4/6 inhibitor(ribociclib) with AR inhibitor(enzalutamide) in the AR-positive TNBC cell line. Ribociclib showed an inhibitory effect in TNBC cells. Additionally, we found that enzalutamide reduced cell migration/invasion, clonogenic capacity, cell cycle progression, and cell growth in AR-positive cells. Enzalutamide therapy could increase the cytostatic impact of ribociclib in AR+ TNBC cells. Furthermore, dual inhibition of AR and CDK4/6 demonstrated synergy in an AR+ TNBC model compared to each treatment alone.
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影响因子：
50.3
作者：
Anders L;Ke N;Hydbring P;Choi YJ;Widlund HR;Chick JM;Zhai H;Vidal M;Gygi SP;Braun P;Sicinski P
通讯作者：
Sicinski P
影响因子：
14.9
作者：
Lanzino M;Sisci D;Morelli C;Garofalo C;Catalano S;Casaburi I;Capparelli C;Giordano C;Giordano F;Maggiolini M;Andò S
通讯作者：
Andò S
影响因子：
5.2
作者：
Rangel N;Villegas VE;Rondón-Lagos M
通讯作者：
Rondón-Lagos M
DOI：
10.1080/21691401.2019.1670670
发表时间：
2019-12-04
影响因子：
5.8
作者：
Li, Tianqi;Xiong, Yudi;Zhou, Yunfeng
通讯作者：
Zhou, Yunfeng
三阴性乳腺癌的多个分子亚型批判性地依赖于雄激素受体，并在体内对enzalutamide反应。
影响因子：
5.7
作者：
Barton VN;D'Amato NC;Gordon MA;Lind HT;Spoelstra NS;Babbs BL;Heinz RE;Elias A;Jedlicka P;Jacobsen BM;Richer JK
通讯作者：
Richer JK