title: Bruton's tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer.
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.
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Gadjah Mada University-Sardjito Central Hospital, Yogyakarta, Indonesia.
authors.forename: Muhammad Ary
authors.initials: MA
authors.lastname: Zucha
authors.affiliation: Graduate Institute of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.|Translational Research Laboratory, Cancer Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Alexander T H
authors.initials: AT
authors.lastname: Wu
authors.affiliation: Department of Pathology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Wei-Hwa
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Liang-Shun
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wan-Wan
authors.initials: WW
authors.lastname: Lin
authors.affiliation: Obstetrics and Gynecology Department, Shuang-Ho Hospital, Taipei, Taiwan.
authors.forename: Chiou-Chung
authors.initials: CC
authors.lastname: Yuan
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Medical Research and Education, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D010880:Piperidines; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D000225:Adenine; D002945:Cisplatin
keywords: Bruton’s tyrosine kinase (Btk); cancer stem cell (CSC); cisplatin; ibrutinib; ovarian cancer; spheroids