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Review
. 2019 Nov 19;11(11):1820.
doi: 10.3390/cancers11111820.

Endometrial Cancer Stem Cells: Role, Characterization and Therapeutic Implications

Gaia Giannone  1   2 , Laura Attademo  3 , Giulia Scotto  1   2 , Sofia Genta  1   2 , Eleonora Ghisoni  1   2 , Valentina Tuninetti  1   2 , Massimo Aglietta  1   2 , Sandro Pignata  3 , Giorgio Valabrega  1   2
Affiliations
Review

Endometrial Cancer Stem Cells: Role, Characterization and Therapeutic Implications

Gaia Giannone et al. Cancers (Basel). .

Abstract

Endometrial cancer (EC) is the most frequent gynecological cancer. In patients with relapsed and advanced disease, prognosis is still dismal and development of resistance is common. In this context, endometrial Cancer Stem Cells (eCSC), stem-like cells capable to self-renewal and differentiation in mature cancer cells, represent a potential field of expansion for drug development. The aim of this review is to characterize the role of eCSC in EC, their features and how they could be targeted. CSC are involved in progression, invasiveness and metastasis (though epithelial to mesenchimal transition, EMT), as well as chemoresistance in EC. Nevertheless, isolation of eCSC is still controversial. Indeed, CD133, Aldheyde dehydrogenase (ALDH), CD117, CD55 and CD44 are enriched in CSCs but there is no universal marker nowadays. The most frequently activated pathways in eCSC are Wingless-INT (Wnt)/β-catenin, Notch1, and Hedghog, with a high expression of self-renewal transcription factors like Octamer binding transcription factor 4 (OCT), B Lymphoma Mo-MLV Insertion Region 1 Homolog (BMI1), North American Network Operations Group Homebox protein (NANOG), and SRY-Box 2 (SOX2). These pathways have been targeted with selective drugs alone or in combination with chemotherapy and immunotherapy. Unfortunately, although preclinical results are encouraging, few clinical data are available.

Keywords: Cancer stem cell; endometrial cancer; target therapy.

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Conflict of interest statement

Giannone reports grants from Roche, outside the submitted work. Attademo, Scotto, Genta, Ghisoni, Tuninetti have nothing to disclose. Aglietta reports travel grant from Merck, Tesaro and BMS, has been part of advisory board of Bayer, Novartis, BMS and Merck, received funding from Astrazeneca and Pharmamar, all outside the submitted work. Pignata reports honoraria from AstraZeneca, Tesaro Clovis, Roche, Pharmamar, MSD, Pfizer and Research funding from AstraZeneca, MSD, Roche Pfizer outside the submitted work. Valabrega reports speaking honoraria from AstraZeneca, Tesaro, Roche, Amgen, PharmaMar and has been part of advisory boards of Tesaro, Amgen and PharmaMar, outside the submitted work.

Figures

Figure 1
Figure 1
Activated pathways in Endometrial Cancer Stem Cells (CSCs) and their inhibitors.
See this image and copyright information in PMC

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