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TP53和PI3K信号通路作为妇科恶性肿瘤分子靶点的特征分析

Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies.

作者信息

Oda Katsutoshi, Ikeda Yuji, Kashiyama Tomoko, Miyasaka Aki, Inaba Kanako, Fukuda Tomohiko, Asada Kayo, Sone Kenbun, Wada-Hiraike Osamu, Kawana Kei, Osuga Yutaka, Fujii Tomoyuki

机构信息

Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

出版信息

J Obstet Gynaecol Res. 2016 Jul;42(7):757-62. doi: 10.1111/jog.13018. Epub 2016 Apr 20.

Abstract

Recent developments in genomic analysis have unveiled the key signaling pathways in human cancer. However, only a limited number of molecular-targeted drugs are applicable for clinical use in gynecologic malignancies. TP53 signaling and phosphatidylinositol 3 kinase pathways are frequently mutated in cancer, and have received much attention as molecular targets in human cancers. In this review, we mainly focus on the functions of these pathways, and discuss the molecular-targeted drugs under clinical trials. The molecular-targeted drugs described in this review include dual phosphatidylinositol 3 kinase/mTOR inhibitors (NVP-BEZ235, DS-7423, SAR245409), an mTOR inhibitor (everolimus), an MEK inhibitor (pimasertib), an autophagy inhibitor (chloroquine), a cyclin-dependent kinases 4/6 inhibitor (PD0332991), and a poly (ADP-ribose) polymerase inhibitor (olaparib).

摘要

基因组分析的最新进展揭示了人类癌症中的关键信号通路。然而,仅有有限数量的分子靶向药物可应用于妇科恶性肿瘤的临床治疗。TP53信号通路和磷脂酰肌醇3激酶通路在癌症中经常发生突变,作为人类癌症的分子靶点受到了广泛关注。在本综述中,我们主要聚焦于这些通路的功能,并讨论正在进行临床试验的分子靶向药物。本综述中描述的分子靶向药物包括双磷脂酰肌醇3激酶/雷帕霉素靶蛋白抑制剂(NVP-BEZ235、DS-7423、SAR245409)、雷帕霉素靶蛋白抑制剂(依维莫司)、丝裂原活化蛋白激酶/细胞外信号调节激酶抑制剂(匹美替尼)、自噬抑制剂(氯喹)、细胞周期蛋白依赖性激酶4/6抑制剂(PD0332991)以及聚(ADP-核糖)聚合酶抑制剂(奥拉帕利)。

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