Regulatory Signaling Pathways in Ovarian Cancer Stem Cells: Their Role in Tumor Progression and Therapeutic Strategies

Authors
Dini Amalia 1
Febriani Febriani 2
Arfianti Arfianti 3
1 Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
2 Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Riau/District General Hospital Arifin Achmad Riau Province, Pekanbaru, Indonesia
3 Department of Medical Biology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia
10.66224/ibj.5158
Abstract
In ovarian cancer, ovarian cancer stem cells (OCSCs) not only contribute to tumor formation but also drive the progression, metastasis, and chemoresistance. The defining properties of OCSCs are sustained through the Wnt/β-catenin, Notch, and Hedgehog signaling pathways, which can synergize rather than act independently to form a triad that enhances key functional capabilities of OCSCs. Various therapeutic agents have been studied to target these pathways in OCSCs, including γ-secretase inhibitors (nirogacestat), smoothened inhibitors (vismodegib and sonidegib), and Wnt/β-catenin inhibitors (PRI-724 and ipafricept). While these agents have demonstrated antitumor activity in preclinical and early clinical studies, their clinical use remains challenging due to compensatory interactions among signaling pathways, which diminish the efficacy of single-agent treatments. To improve treatment outcomes, strategies involving combination approaches and personalized treatments need to be explored. This review aims to summarize current evidence on the role of Wnt/β-catenin, Notch, and Hedgehog signaling pathways in OCSCs and their therapeutic implications in ovarian cancer.
Keywords
Hedgehogs
Ovarian Neoplasms
Therapeutics
WNT Signaling Pathway