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Published on: March 1, 2020
Therapeutic and Prognostic Relevance of Cancer Stem Cell Populations in Endometrial Cancer: A Narrative Review
Ioana Cristina Rotar1, Elena Bernad2,3, Liviu Moraru4
1Obstetrics and Gynecology I, Mother and Child Department, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Abstract:
The biggest challenge in cancer therapy is tumor resistance to the classical approach. Thus, research interest has shifted toward the cancer stem cell population (CSC). CSCs are a small subpopulation of cancer cells within tumors with self-renewal, differentiation, and metastasis/malignant potential. They are involved in tumor initiation and development, metastasis, and recurrence.
Method:
A narrative review of significant scientific publications related to the topic and its applicability in endometrial cancer (EC) was performed with the aim of identifying current knowledge about the identification of CSC populations in endometrial cancer, their biological significance, prognostic impact, and therapeutic targeting.
Results:
Therapy against the tumor population alone has no or negligible effect on CSCs. CSCs, due to their stemness and therapeutic resistance, cause tumor relapse. They target CSCs that may lead to noticeable persistent tumoral regression. Also, they can be used as a predictive marker for poor prognosis. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that the cultured cells strongly expressed stemness-related genes, such as SOX-2 (sex-determining region Y-box 2), NANOG (Nanog homeobox), and Oct 4 (octamer-binding protein 4). The expression of surface markers CD133+ and CD44+ was found on CSC as stemness markers. Along with surface markers, transcription factors such as NF-kB, HIF-1a, and b-catenin were also considered therapeutic targets. Hypoxia is another vital feature of the tumor environment and aids in the maintenance of the stemness of CSCs. This involves the hypoxic activation of the WNT/b-catenin pathway, which promotes tumor survival and metastasis. Specific antibodies have been investigated against CSC markers; for example, anti-CD44 antibodies have been demonstrated to have potential against different CSCs in preclinical investigations. Anti-CD-133 antibodies have also been developed. Targeting the CSC microenvironment is a possible drug target for CSCs. Focusing on stemness-related genes, such as the transcription pluripotency factors SOX2, NANOG, and OCT4, is another therapeutic option.
Conclusions:
Stemness surface and gene markers can be potential prognostic biomarkers and management approaches for cases with drug-resistant endometrial cancers.
Insights
Cancer stem cells (CSCs) drive tumor resistance and recurrence. Targeting CSCs and their markers, like SOX-2, NANOG, and OCT4, offers a promising therapeutic strategy for endometrial cancer, potentially improving patient prognosis.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Medicine
Background:
- Tumor resistance to conventional therapies presents a significant challenge in cancer treatment.
- Cancer stem cells (CSCs) are a critical subpopulation responsible for tumor initiation, metastasis, and recurrence due to their self-renewal and differentiation capabilities.
- CSCs exhibit inherent resistance to standard therapies, contributing to treatment failure and disease relapse.
Purpose of the Study:
- To review current knowledge on the identification, biological significance, and prognostic impact of CSCs in endometrial cancer (EC).
- To explore the therapeutic targeting strategies for CSCs in EC.
- To evaluate the potential of CSC markers as prognostic biomarkers and therapeutic targets.
Main Methods:
- A narrative review of scientific literature focusing on CSCs in endometrial cancer.
- Analysis of studies investigating CSC identification, biological roles, and therapeutic approaches.
- Examination of gene expression (SOX-2, NANOG, Oct 4) and surface marker (CD133+, CD44+) data related to CSCs.
Main Results:
- Conventional therapies are largely ineffective against CSCs, which drive tumor relapse.
- CSCs express stemness-related genes (SOX-2, NANOG, Oct 4) and surface markers (CD133+, CD44+).
- Therapeutic strategies targeting CSCs, their markers (e.g., anti-CD44, anti-CD133 antibodies), and microenvironment (hypoxia, WNT/b-catenin pathway) show potential for persistent tumor regression and improved prognosis.
Conclusions:
- Stemness surface and gene markers are valuable prognostic biomarkers in drug-resistant endometrial cancers.
- Targeting CSCs and their associated pathways represents a viable therapeutic strategy for improving outcomes in endometrial cancer.
- Further research into CSC-specific therapies is crucial for overcoming treatment resistance and preventing recurrence.
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