pci-32765 and Ovarian-Neoplasms

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.

Topics: Adenine; Adult; Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; Cisplatin; Drug Resistance, Neoplasm; Drug Therapy, Combination; Female; Humans; Janus Kinase 2; Middle Aged; Neoplastic Stem Cells; Ovarian Neoplasms; Piperidines; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines; STAT3 Transcription Factor; Young Adult