Sobočan Monika, Bračič Suzana, Knez Jure, Takač Iztok, Haybaeck Johannes
Department of Pharmacology, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia.
Divison of Gynecology and Perinatology, University Medical Centre Maribor, 2000 Maribor, Slovenia.
Cancers (Basel). 2020 Jan 14;12(1):205. doi: 10.3390/cancers12010205.
Studies of the mechanistic (mammalian) target of rapamycin inhibitors (mTOR) represent a step towards the targeted treatment of gynecological cancers. It has been shown that women with increased levels of mTOR signaling pathway targets have worse prognosis compared to women with normal mTOR levels. Yet, targeting mTOR alone has led to unsatisfactory outcomes in gynecological cancer. The aim of our review was therefore to provide an overview of the most recent clinical results and basic findings on the interplay of mTOR signaling and cold shock proteins in gynecological malignancies. Due to their oncogenic activity, there are promising data showing that mTOR and Y-box-protein 1 (YB-1) dual targeting improves the inhibition of carcinogenic activity. Although several components differentially expressed in patients with ovarian, endometrial, and cervical cancer of the mTOR were identified, there are only a few investigated downstream actors in gynecological cancer connecting them with YB-1. Our analysis shows that YB-1 is an important player impacting AKT as well as the downstream actors interacting with mTOR such as epidermal growth factor receptor (EGFR), Snail or E-cadherin.
雷帕霉素抑制剂(mTOR)的机制性(哺乳动物)靶点研究是妇科癌症靶向治疗的一个进展。研究表明,与mTOR水平正常的女性相比,mTOR信号通路靶点水平升高的女性预后更差。然而,单独靶向mTOR在妇科癌症中并未取得令人满意的结果。因此,我们综述的目的是概述mTOR信号与冷休克蛋白在妇科恶性肿瘤中相互作用的最新临床结果和基础研究发现。由于其致癌活性,有前景的数据表明,mTOR和Y盒蛋白1(YB-1)双重靶向可增强对致癌活性的抑制作用。虽然在卵巢癌、子宫内膜癌和宫颈癌患者中鉴定出了mTOR的几种差异表达成分,但在妇科癌症中,将它们与YB-1联系起来的下游作用因子仅有少数得到研究。我们的分析表明,YB-1是影响AKT以及与mTOR相互作用的下游作用因子(如表皮生长因子受体(EGFR)、Snail或E-钙黏蛋白)的重要因素。