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.
Highlights
Endometrial cancer (EC) is the most common gynecological tumor in developed countries
The aim of this review is to describe the role of cancer stem cells (CSCs) in EC, their features, the most frequently involved pathways and how they could be targeted on the basis of preclinical evidence and clinical studies
High expression of Aldehyde dehydrogenase 1 (ALDH1) correlates with a worse prognosis in EC patients (p = 0.01 for Overall Survival (OS)) [83]
Summary
Endometrial cancer (EC) is the most common gynecological tumor in developed countries. Known risk factors are early menarche, late menopause, polycystic ovary syndrome (PCOS), infertility, obesity and diabetes genetic predisposition with presence of Lynch Syndrome is fundamental in patients with diagnosis before the age of 50 [3,4,5]. Almost 80% of EC type I patients had lower grade (G1 or G2) tumors, while 20% had high grade (G3) tumors [6]. They usually have low potential for lymphovascular invasion, high estrogen (ER) and progesterone receptors (PgR) expression, and a favorable prognosis [6]. Type II EC is characterized by prevalence of high grade (G3)
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