Novel Targets for Ovarian Cancer Stem Cells

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About this Research Topic

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Background

Ovarian cancer (OC) is an aggressive cancer and is the second most lethal gynecological cancer in women, with the highest rates of recurrence and mortality. Poor outcomes are partially associated with late stage at diagnosis and acquired drug resistance. Although significant progress has been made in diagnosis and the development of precisely targeted and systemic therapy, cytoreductive surgery and platinum‐based chemotherapy remain the front-line treatment for women with OC. Emerging evidence indicates that chemotherapy is effective in debulking ovarian tumors; however, residuals persist and are enriched in cancer stem cells (CSCs). CSCs are a rare population of cells which are able to repopulate tumors and drive tumor recurrence. Thus, there is a critical need to develop novel strategies to eliminate this population and improve long‐term survival rates for OC patients.

The persistence of CSCs after chemotherapy has been hypothesized to be responsible for tumor relapse in many solid tumors, including OC. Ovarian CSCs have been isolated from established OC cell lines, ascites and primary ovarian tumors, with a phenotype associated with drug resistance. Several markers have been proposed for ovarian CSC identification and isolation, including CD133+/ALDH+, ALDH+ and CD44+/CD117+. Similarly to embryonic stem cells, ovarian CSCs also exhibit enhanced self-renewal ability, tumor initiating capacity, and expression of “stemness”-associated transcription factors. Significant challenges still persist in understanding the epigenetic, genetic and metabolic signatures contributing to stemness maintenance of ovarian CSCs, due to heterogenicity of this population and technical barriers related to its scarcity. In this field of research, it is hypothesized that targeting these stemness features could eradicate CSCs responsible for tumor relapse. The goals of this collection are to define stemness-associated vulnerabilities, and to contribute to the discovery of new therapies to eradicate tumorigenic CSCs, reverse chemo-resistance and prevent tumor relapse for women with OC.

This section will discuss current advances and new directions for targeting ovarian CSCs. Any Original Research, Review on Mini-Review manuscripts approaching research questions on the following topics are welcome:
1. Genomics: understanding genetic and molecular signaling for stemness maintenance in ovarian CSCs
2. Epigenomics: defining epigenetic signatures of ovarian CSCs and discovering novel epigenetic targets for ovarian CSCs
3. Metabolic adaptions: defining novel metabolic adaptions associated with stemness of ovarian CSCs
4. Biomarkers: identifying novel markers for ovarian CSCs identification and isolation
5. Single cell RNA-Sequencing analysis: identifying heterogenicity of ovarian CSCs population
6. Developing new animal models for assessing tumorigenicity and self-renewal ability of ovarian CSCs
7. Novel therapeutic approaches for targeting ovarian CSCs
8. New theories regarding the tumor microenvironment, and anti-tumor immune response contributing to ovarian CSC targeting or maintenance

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: ovarian cancer, epigenetics, Cancer Stem Cells, metabolic adaptation, targeted therapy

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