Experimental Therapy of Advanced Breast Cancer: Targeting NFAT1-MDM2-p53 Pathway.
Experimental Therapy of Advanced Breast Cancer: Targeting NFAT1-MDM2-p53 Pathway.
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DOI：
10.1016/bs.pmbts.2017.07.005
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发表时间：
2017
影响因子：
--
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Qin JJ;Wang W;Zhang R
晚期乳腺癌，特别是晚期三阴性乳腺癌，通常比其他乳腺癌表型更具侵袭性，也更难治疗。目前，患有晚期疾病的乳腺癌患者还没有可治愈的选择，这突显了对新的治疗策略的迫切需要。我们最近发现，活化的T细胞核因子1(NFAT1)激活了小鼠双分钟2(MDM2)癌基因。MDM2和NFAT1在乳腺癌中均有过度表达，在乳腺癌中呈结构性激活，尤其在晚期乳腺癌中，ANC参与其发生、发展和转移。MDM2通过P53依赖和非依赖机制调控癌细胞的增殖、细胞周期进程、细胞凋亡、迁移和侵袭。我们已经提出以NFAT1-MDM2-P53通路为靶点来治疗人类癌症，特别是乳腺癌。我们最近发现了NFAT1和MDM2双重抑制物，它们在体外和体内对乳腺癌(包括三阴性乳腺癌)都表现出了良好的活性。在此，我们综述了在理解MDM2和NFAT1在乳腺癌中的致癌作用方面的最新进展，以及当前的靶向策略和代表性的抑制剂。我们还提出了抑制NFAT1-MDM2-P53通路的几种策略，这些策略可能有助于开发更特异和有效的乳腺癌治疗抑制剂。
Advanced breast cancer, especially advanced triple-negative breast cancer, is typically more aggressive and more difficult to treat than other breast cancer phenotypes. There is currently no curable option for breast cancer patients with advanced diseases, highlighting the urgent need for novel treatment strategies. We have recently discovered that the nuclear factor of activated T cells 1 (NFAT1) activates the murine double minute 2 (MDM2) oncogene. Both MDM2 and NFAT1 are overexpressed ancconstitutively activated in breast cancer, particularly in advanced breast cancer, anc contribute to its initiation, progression, and metastasis. MDM2 regulates cancer cell proliferation, cell cycle progression, apoptosis, migration, and invasion through both p53-dependent and-independent mechanisms. We have proposed to target the NFAT1–MDM2–p53 pathway for the treatment of human cancers, especially breast cancer. We have recently identified NFAT1 and MDM2 dual inhibitors that have shown excellent in vitro and in vivo activities against breast cancer, including triple-negative breast cancer. Herein, we summarize recent advances made in the understanding of the oncogenic functions of MDM2 and NFAT1 in breast cancer, as well as current targeting strategies and representative inhibitors. We also propose several strategies for inhibiting the NFAT1–MDM2–p53 pathway, which could be useful for developing more specific and effective inhibitors for breast cancer therapy.
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MDM2/X 靶向治疗的临床概述。
影响因子：
4.7
作者：
Burgess A;Chia KM;Haupt S;Thomas D;Haupt Y;Lim E
通讯作者：
Lim E
影响因子：
5.7
作者：
Baumgart S;Chen NM;Zhang JS;Billadeau DD;Gaisina IN;Kozikowski AP;Singh SK;Fink D;Ströbel P;Klindt C;Zhang L;Bamlet WR;Koenig A;Hessmann E;Gress TM;Ellenrieder V;Neesse A
通讯作者：
Neesse A
影响因子：
29.4
作者：
Baumgart S;Glesel E;Singh G;Chen NM;Reutlinger K;Zhang J;Billadeau DD;Fernandez-Zapico ME;Gress TM;Singh SK;Ellenrieder V
通讯作者：
Ellenrieder V
DOI：
10.1007/bf01535205
发表时间：
1987-05-01
期刊：
SOMATIC CELL AND MOLECULAR GENETICS
影响因子：
--
作者：
CAHILLYSNYDER, L;YANGFENG, T;GEORGE, DL
通讯作者：
GEORGE, DL
影响因子：
8
作者：
Chen, M;O'Connor, KL
通讯作者：
O'Connor, KL