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Can Stemness and Chemoresistance Be Therapeutically Targeted via Signaling Pathways in Ovarian Cancer?

by Lynn Roy 1,2 and Karen D. Cowden Dahl 1,2,3,4,*
Harper Cancer Research Institute, South Bend, IN 46617, USA
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, South Bend, IN 46617, USA
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46617, USA
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN 46202, USA
Author to whom correspondence should be addressed.
Cancers 2018, 10(8), 241;
Received: 15 June 2018 / Revised: 12 July 2018 / Accepted: 17 July 2018 / Published: 24 July 2018
(This article belongs to the Special Issue The Tumor Microenvironment of High Grade Serous Ovarian Cancer)
Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, is often attributed to late stage at diagnosis and relapse following chemotherapy. HGS ovarian cancer is a heterogenous disease in that few genes are consistently mutated between patients. Additionally, HGS ovarian cancer is characterized by high genomic instability. For these reasons, personalized approaches may be necessary for effective treatment and cure. Understanding the molecular mechanisms that contribute to tumor metastasis and chemoresistance are essential to improve survival rates. One favored model for tumor metastasis and chemoresistance is the cancer stem cell (CSC) model. CSCs are cells with enhanced self-renewal properties that are enriched following chemotherapy. Elimination of this cell population is thought to be a mechanism to increase therapeutic response. Therefore, accurate identification of stem cell populations that are most clinically relevant is necessary. While many CSC identifiers (ALDH, OCT4, CD133, and side population) have been established, it is still not clear which population(s) will be most beneficial to target in patients. Therefore, there is a critical need to characterize CSCs with reliable markers and find their weaknesses that will make the CSCs amenable to therapy. Many signaling pathways are implicated for their roles in CSC initiation and maintenance. Therapeutically targeting pathways needed for CSC initiation or maintenance may be an effective way of treating HGS ovarian cancer patients. In conclusion, the prognosis for HGS ovarian cancer may be improved by combining CSC phenotyping with targeted therapies for pathways involved in CSC maintenance. View Full-Text
Keywords: ovarian cancer; cancer stem cells; signaling; chemoresistance; metastasis ovarian cancer; cancer stem cells; signaling; chemoresistance; metastasis
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Roy, L.; Cowden Dahl, K.D. Can Stemness and Chemoresistance Be Therapeutically Targeted via Signaling Pathways in Ovarian Cancer? Cancers 2018, 10, 241.

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