Abstract
According to a Prognoscan database, upregulation of Bruton's tyrosine kinase (Btk) is associated with low overall survival in ovarian cancer patients. We found that spheroids-forming ovarian cancer cell, which highly expressed cancer stem-like cell (CSC) markers and Btk, were cisplatin resistant. We next treated CSCs and non-CSCs by a combination of ibrutinib and cisplatin. We found that chemoresistance was dependent on Btk and JAK2/STAT3, which maintained CSC by inducing Sox-2 and prosurvival genes. We suggest that addition of ibrutinib to cisplatin may improve treatment outcome in ovarian cancer.
Highlights
Ovarian cancer is the fourth most common malignancy in women and is the leading cause of death from gynecological cancers [1]
We showed that chemoresistant ovarian cancer cell lines highly expressed cancer stem-like cell (CSC) regulatory genes
Ovarian spheroids enriched with CSCs were more resistant to cisplatin when the Bruton’s tyrosine kinase (Btk) signaling pathway was activated
Summary
Ovarian cancer is the fourth most common malignancy in women and is the leading cause of death from gynecological cancers [1]. Ninety-two percent of ovarian cancer patients in stage I have a 5-year survival. Patients diagnosed in the late stage have poor prognosis, with only 19% of 5-year survival rate for stage IV patients [1, 4]. Because ovarian cancer exhibits this clinical behavior, developing an effective treatment strategy for late-stage ovarian cancer patients is crucial. The current standard first-line treatment for late-stage ovarian cancer, which includes a combination of cytoreductive surgery and platinum-based chemotherapy, usually yields a multiyear survival rate, prolonged use of platinum-based chemotherapy usually induces drug resistance. It is crucial to develop a novel drug that effectively impacts on ovarian cancer especially that is resistant to current chemotherapy [4, 6]
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