Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells

Notch signaling is frequently activated in ovarian cancer (OC) and contributes to the proliferation and survival of cultured OC cells as well as to tumor formation and angiogenesis in xenograft models. Several studies demonstrate that Notch3 expression renders cancer cells more resistant to carbopla...

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Main Authors: Simona Ceccarelli, Francesca Megiorni, Diana Bellavia, Cinzia Marchese, Isabella Screpanti, Saula Checquolo
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/6264931
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author Simona Ceccarelli
Francesca Megiorni
Diana Bellavia
Cinzia Marchese
Isabella Screpanti
Saula Checquolo
author_facet Simona Ceccarelli
Francesca Megiorni
Diana Bellavia
Cinzia Marchese
Isabella Screpanti
Saula Checquolo
author_sort Simona Ceccarelli
collection DOAJ
description Notch signaling is frequently activated in ovarian cancer (OC) and contributes to the proliferation and survival of cultured OC cells as well as to tumor formation and angiogenesis in xenograft models. Several studies demonstrate that Notch3 expression renders cancer cells more resistant to carboplatin, contributing to chemoresistance and poor survival of OC-bearing patients. This suggests that Notch3 can represent both a biomarker and a target for therapeutic interventions in OC patients. Although it is still unclear how chemoresistance arises, different lines of evidence support a critical role of cancer stem cells (CSCs), suggesting that CSC targeting by innovative therapeutic approaches might represent a promising tool to efficiently reduce OC recurrence. To date, CSC-directed therapies in OC tumors are mainly targeted to the inhibition of CSC-related signaling pathways, including Notch. As it is increasingly evident the involvement of Notch signaling, and in particular of Notch3, in regulating stem-like cell maintenance and expansion in several tumors, here we provide an overview of the current knowledge of Notch3 role in CSC-mediated OC chemoresistance, finally exploring the potential design of innovative Notch3 inhibition-based therapies for OC treatment, aimed at eradicating tumor through the suppression of CSCs.
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language English
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series Stem Cells International
spelling doaj-art-2be4a876d9614aa8bfa50238a13c45fb2025-08-20T02:04:49ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/62649316264931Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem CellsSimona Ceccarelli0Francesca Megiorni1Diana Bellavia2Cinzia Marchese3Isabella Screpanti4Saula Checquolo5Department of Experimental Medicine, “Sapienza” University of Rome, Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, Rome, ItalyDepartment of Molecular Medicine, “Sapienza” University of Rome, Rome, ItalyDepartment of Experimental Medicine, “Sapienza” University of Rome, Rome, ItalyDepartment of Molecular Medicine, “Sapienza” University of Rome, Rome, ItalyDepartment of Medico-Surgical Sciences and Biotechnology, Sapienza University, Latina, ItalyNotch signaling is frequently activated in ovarian cancer (OC) and contributes to the proliferation and survival of cultured OC cells as well as to tumor formation and angiogenesis in xenograft models. Several studies demonstrate that Notch3 expression renders cancer cells more resistant to carboplatin, contributing to chemoresistance and poor survival of OC-bearing patients. This suggests that Notch3 can represent both a biomarker and a target for therapeutic interventions in OC patients. Although it is still unclear how chemoresistance arises, different lines of evidence support a critical role of cancer stem cells (CSCs), suggesting that CSC targeting by innovative therapeutic approaches might represent a promising tool to efficiently reduce OC recurrence. To date, CSC-directed therapies in OC tumors are mainly targeted to the inhibition of CSC-related signaling pathways, including Notch. As it is increasingly evident the involvement of Notch signaling, and in particular of Notch3, in regulating stem-like cell maintenance and expansion in several tumors, here we provide an overview of the current knowledge of Notch3 role in CSC-mediated OC chemoresistance, finally exploring the potential design of innovative Notch3 inhibition-based therapies for OC treatment, aimed at eradicating tumor through the suppression of CSCs.http://dx.doi.org/10.1155/2019/6264931
spellingShingle Simona Ceccarelli
Francesca Megiorni
Diana Bellavia
Cinzia Marchese
Isabella Screpanti
Saula Checquolo
Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells
Stem Cells International
title Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells
title_full Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells
title_fullStr Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells
title_full_unstemmed Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells
title_short Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells
title_sort notch3 targeting a novel weapon against ovarian cancer stem cells
url http://dx.doi.org/10.1155/2019/6264931
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AT francescamegiorni notch3targetinganovelweaponagainstovariancancerstemcells
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AT cinziamarchese notch3targetinganovelweaponagainstovariancancerstemcells
AT isabellascrepanti notch3targetinganovelweaponagainstovariancancerstemcells
AT saulachecquolo notch3targetinganovelweaponagainstovariancancerstemcells