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Updated: May 18, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer
Mohammed Tanjimur Rahman1, Kentaro Nakayama, Munmun Rahman
1Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan.
Abstract:
This study examined the clinical significance of Notch3 expression and assessed its usefulness as a potential therapeutic target in chemoresistant ovarian cancer. Notch3 expression was assessed with immunohistochemical examination, and clinical variables were collected with a retrospective chart review. Notch3 siRNA or γ-secretase inhibitor was used to assess Notch3 function in ovarian cancer cell lines. Notch3 overexpression correlated with shorter progression-free/overall survival in patients with advanced stage (stage III, IV) ovarian carcinoma treated with platinum and taxane. Three of 5 patients showed increased Notch3 immunostaining in recurrent tumors compared with corresponding primary tumors. Notch3 overexpression was observed in both the cisplatin-resistant KFr13 and cisplatin/paclitaxel-resistant KFr13Tx cells. Inactivation of Notch3 by γ-secretase inhibitor or siRNA decreased cell proliferation and induced apoptosis in the KFr13 and KFr13Tx cells. Our findings suggest that Notch3 expression may be related to chemoresistance and that the Notch3 pathway may represent a novel therapeutic target for advanced stage chemoresistant ovarian cancer.
Insights
Notch3 overexpression is linked to poorer survival and chemoresistance in advanced ovarian cancer. Inhibiting Notch3 shows promise as a new therapeutic strategy for treating this difficult-to-treat cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Ovarian cancer remains a leading cause of cancer-related death.
- Chemoresistance significantly limits treatment efficacy in advanced ovarian cancer.
- The role of Notch3 signaling in ovarian cancer progression and treatment resistance is not well understood.
Purpose of the Study:
- To investigate the clinical significance of Notch3 expression in ovarian cancer.
- To evaluate Notch3 as a potential therapeutic target in chemoresistant ovarian cancer.
- To explore the functional role of Notch3 in ovarian cancer cell lines.
Main Methods:
- Immunohistochemical examination of Notch3 expression in patient tumors.
- Retrospective chart review of clinical variables.
- In vitro studies using Notch3 siRNA and a gamma-secretase inhibitor in ovarian cancer cell lines.
Main Results:
- Notch3 overexpression correlated with shorter progression-free and overall survival in advanced ovarian cancer patients treated with platinum and taxane.
- Increased Notch3 immunostaining was observed in recurrent tumors compared to primary tumors in a subset of patients.
- Inactivation of Notch3 reduced proliferation and induced apoptosis in chemoresistant ovarian cancer cell lines.
Conclusions:
- Notch3 expression is associated with chemoresistance and poorer clinical outcomes in advanced ovarian cancer.
- The Notch3 pathway represents a potential novel therapeutic target for overcoming chemoresistance in ovarian cancer.
- Targeting Notch3 may offer a new strategy for treating advanced, treatment-resistant ovarian cancer.
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