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妇科癌症中mTOR通路抑制剂的综述

A Review of mTOR Pathway Inhibitors in Gynecologic Cancer.

作者信息

de Melo Andréia Cristina, Paulino Eduardo, Garces Álvaro Henrique Ingles

机构信息

Brazilian National Cancer Institute (INCA), Rio de Janeiro, RJ, Brazil.

出版信息

Oxid Med Cell Longev. 2017;2017:4809751. doi: 10.1155/2017/4809751. Epub 2017 Feb 13.

Abstract

The treatment of advanced gynecologic cancers remains palliative in most of cases. Although systemic treatment has entered into the era of targeted drugs the antitumor efficacies of current therapies are still limited. In this context there is a great need for more active treatment and rationally designed targeted therapies. The PI3K/AKT/mTOR is a signaling pathway in mammal cells that coordinates important cell activities. It has a critical function in the survival, growth, and proliferation of malignant cells and was object of important research in the last two decades. The mTOR pathway emerges as an attractive therapeutic target in cancer because it serves as a convergence point for many growth stimuli and, through its downstream substrates, controls cellular processes that contribute to the initiation and maintenance of cancer. Aberrant PI3K-dependent signaling occurs frequently in a wide range of tumor types, including endometrial, cervical, and ovarian cancers. The present study reviewed the available evidence regarding the potential impact of some mTOR pathway inhibitors in the treatment of gynecological cancer. Few advances in medical management have occurred in recent years in the treatment of advanced or recurrent gynecological malignancies, and a poor prognosis remains. Rationally designed molecularly targeted therapy is an emerging and important option in this setting; then more investigation in PI3K/AKT/mTOR pathway-targeted therapies is warranted.

摘要

在大多数情况下,晚期妇科癌症的治疗仍以姑息治疗为主。尽管全身治疗已进入靶向药物时代,但目前疗法的抗肿瘤疗效仍然有限。在此背景下,迫切需要更积极的治疗和合理设计的靶向疗法。PI3K/AKT/mTOR是哺乳动物细胞中的一条信号通路,可协调重要的细胞活动。它在恶性细胞的存活、生长和增殖中起关键作用,是过去二十年重要的研究对象。mTOR通路作为癌症中一个有吸引力的治疗靶点出现,因为它是许多生长刺激的汇聚点,并通过其下游底物控制有助于癌症发生和维持的细胞过程。异常的PI3K依赖性信号传导在包括子宫内膜癌、宫颈癌和卵巢癌在内的多种肿瘤类型中频繁发生。本研究综述了一些mTOR通路抑制剂在妇科癌症治疗中潜在影响的现有证据。近年来,晚期或复发性妇科恶性肿瘤的治疗在医学管理方面进展甚微,预后仍然很差。合理设计的分子靶向治疗在这种情况下是一种新兴且重要的选择;因此,有必要对PI3K/AKT/mTOR通路靶向治疗进行更多研究。

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