Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies
Characterization of TP53 and PI3K signaling pathways as molecular targets in gynecologic malignancies
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DOI：
10.1111/jog.13018
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发表时间：
2016-07-01
影响因子：
1.6
通讯作者：
Fujii, Tomoyuki
中科院分区：
文献类型：
--
作者：
Oda, Katsutoshi;Ikeda, Yuji;Fujii, Tomoyuki
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，只有有限数量的分子靶向药物适用于妇科恶性肿瘤的临床使用。TP 53信号传导和磷脂酰肌醇3激酶途径在癌症中经常突变，并且作为人类癌症的分子靶点而受到广泛关注。本文主要对这些通路的功能进行综述，并对正在进行临床试验的分子靶向药物进行讨论。本综述中描述的分子靶向药物包括磷脂酰肌醇3激酶/mTOR双重抑制剂（NVP-BEZ 235、DS-7423、SAR 245409）、mTOR抑制剂（依维莫司）、MEK抑制剂（匹马塞替）、自噬抑制剂（氯喹）、细胞周期蛋白依赖性激酶4/6抑制剂（PD 0332991）和聚（ADP-核糖）聚合酶抑制剂（奥拉帕尼）。
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).