Preprint Review Version 1 This version is not peer-reviewed

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

Version 1 : Received: 15 June 2018 / Approved: 15 June 2018 / Online: 15 June 2018 (15:14:22 CEST)

A peer-reviewed article of this Preprint also exists.

Roy, L.; Cowden Dahl, K.D. Can Stemness and Chemoresistance Be Therapeutically Targeted via Signaling Pathways in Ovarian Cancer? Cancers 2018, 10, 241. Roy, L.; Cowden Dahl, K.D. Can Stemness and Chemoresistance Be Therapeutically Targeted via Signaling Pathways in Ovarian Cancer? Cancers 2018, 10, 241.

Journal reference: Cancers 2018, 10, 241
DOI: 10.3390/cancers10080241

Abstract

Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, are 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 targeted 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.

Subject Areas

ovarian cancer; cancer stem cells; signaling, chemoresistance, metastasis

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