Carlotta Sabini1, Flavia Sorbi1, Paula Cunnea2,3, Christina Fotopoulou4,5. 1. Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, 50134, Florence, Italy. 2. West London Gynecological Cancer Centre, Imperial College NHS Trust, London, W12 OHS, UK. 3. Department of Surgery and Cancer, Imperial College London, Du Cane Road, London, W12 0HS, UK. 4. West London Gynecological Cancer Centre, Imperial College NHS Trust, London, W12 OHS, UK. chfotopoulou@gmail.com. 5. Department of Surgery and Cancer, Imperial College London, Du Cane Road, London, W12 0HS, UK. chfotopoulou@gmail.com.
Abstract
INTRODUCTION: The role of cancer stem cells (CSC) remains controversial and increasingly subject of investigation as a potential oncogenetic platform with promising therapeutic implications. Understanding the role of CSCs in a highly heterogeneous disease like epithelial ovarian cancer (EOC) may potentially lead to the better understanding of the oncogenetic and metastatic pathways of the disease, but also to develop novel strategies against its progression and platinum resistance. METHODS: We have performed a review of all relevant literature that addresses the oncogenetic potential of stem cells in EOC, their mechanisms, and the associated therapeutic targets. RESULTS: Cancer stem cells (CSCs) have been reported to be implicated not only in the development and pathways of intratumoral heterogeneity (ITH), but also potentially modulating the tumor microenvironment, leading to the selection of sub-clones resistant to chemotherapy. Furthermore, it appears that the enhanced DNA repair abilities of CSCs are connected with their endurance and resistance maintaining their genomic integrity during novel targeted treatments such as PARP inhibitors, allowing them to survive and causing disease relapse functioning as a tumor seeds. CONCLUSIONS: It appears that CSCs play a major role in the underlying mechanisms of oncogenesis and development of relapse in EOC. Part of promising future plans would be to not only use them as therapeutic targets, but also extent their value on a preventative level through engineering mechanisms and prevention of EOC in its origin.
INTRODUCTION: The role of cancer stem cells (CSC) remains controversial and increasingly subject of investigation as a potential oncogenetic platform with promising therapeutic implications. Understanding the role of CSCs in a highly heterogeneous disease like epithelial ovarian cancer (EOC) may potentially lead to the better understanding of the oncogenetic and metastatic pathways of the disease, but also to develop novel strategies against its progression and platinum resistance. METHODS: We have performed a review of all relevant literature that addresses the oncogenetic potential of stem cells in EOC, their mechanisms, and the associated therapeutic targets. RESULTS:Cancer stem cells (CSCs) have been reported to be implicated not only in the development and pathways of intratumoral heterogeneity (ITH), but also potentially modulating the tumor microenvironment, leading to the selection of sub-clones resistant to chemotherapy. Furthermore, it appears that the enhanced DNA repair abilities of CSCs are connected with their endurance and resistance maintaining their genomic integrity during novel targeted treatments such as PARP inhibitors, allowing them to survive and causing disease relapse functioning as a tumor seeds. CONCLUSIONS: It appears that CSCs play a major role in the underlying mechanisms of oncogenesis and development of relapse in EOC. Part of promising future plans would be to not only use them as therapeutic targets, but also extent their value on a preventative level through engineering mechanisms and prevention of EOC in its origin.
Entities:
Keywords:
Epithelial–mesenchymal transition; Ovarian cancer; Stem cells; Very small embryonic-like stem cells
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