Abstract
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.
Highlights
Malignancies of the endometrium, cervix, and ovaries represent the most common gynecological malignancies
While we have observed that Y-box-protein 1 (YB-1) influences vascular endothelial growth factor (VEGF), our observation of the communication of cancer-associated fibroblasts (CAFs) with the overexpression of interleukin (IL-6), Il-8, RANTES, and VEGF needs to be further evaluated in light of data showing the involvement of YB-1
As YB-1 is implicated to act upon AKT expression, the process and interconnection with mTORC2 must be further investigated
Summary
Malignancies of the endometrium, cervix, and ovaries represent the most common gynecological malignancies. The overexpression of mTOR or protein kinase B (more commonly referred to as Akt) was not associated with specific histological subtype features of the tumor [3] This led to the development and clinical testing of mTOR inhibitors in gynecological cancers. Recent studies in colorectal cancer showed that combining strategies of silencing a dual target, YB-1 through the inhibition of p90 ribosomal S6 kinase (RSK) and Akt, lead to improved sensitivity to standard systemic therapy [7]. This warrants the attempt to connect and understand the impactful molecular mechanisms behind the signaling. Clinical Investigation into mTOR Signaling and Inhibition in Women with Gynecological
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