title: Ibrutinib-A double-edge sword in cancer and autoimmune disorders.
abstract: Targeted therapies have appeared as new treatment options for several disease types, including cancer and autoimmune disorders. Of several targets, tyrosine kinases (TKs) are among the most promising. Overexpression of TKs provides a target for novel therapeutic agents, including small molecule inhibitors of tyrosine kinases (TKI). Ibrutinib (PCI-32765) is a TKI of Bruton's tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells. In addition to inhibitory effects, recent studies have shown that ibrutinib has multiple immunomodulatory effects. It binds covalently to IL-2 inducible tyrosine kinase (Itk) in T lymphocytes and suppresses the survival of T-helper (Th) 2 cells. This changes the balance of Th1/Th2 cells toward Th1 subset, which are the main immune cells targeting tumor cells. The dual activity of ibrutinib has paid a great attention and several studies are evaluating the anti-tumor and immunomodulatory effects in cancer, autoimmune disorders and infectious diseases. In this article we review the inhibitory and immunomodulatory effects of ibrutinib in B-cell malignancies, autoimmune diseases and infections, as well as the communication between the Ror1 receptor tyrosine kinase and BCR and effects of ibrutinib on this crosstalk.
authors.affiliation: a Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences , Semnan , Iran .|b Department of Oncology-Pathology, Immune and Gene therapy Lab , Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute , Stockholm , Sweden .
authors.forename: Parviz
authors.initials: P
authors.lastname: Kokhaei
authors.affiliation: c Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Farhad
authors.initials: F
authors.lastname: Jadidi-Niaragh
authors.affiliation: d Research Center for Non-Communicable Diseases, Jahrom University of Medical, Sciences , Jahrom , Iran .
authors.forename: Abdolreza
authors.initials: A
authors.lastname: Sotoodeh Jahromi
authors.affiliation: b Department of Oncology-Pathology, Immune and Gene therapy Lab , Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute , Stockholm , Sweden .|e Departments of Hematology and Oncology , Karolinska University Hospital Solna , Stockholm , Sweden , and.
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
authors.affiliation: b Department of Oncology-Pathology, Immune and Gene therapy Lab , Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute , Stockholm , Sweden .|e Departments of Hematology and Oncology , Karolinska University Hospital Solna , Stockholm , Sweden , and.
authors.forename: Håkan
authors.initials: H
authors.lastname: Mellstedt
authors.affiliation: b Department of Oncology-Pathology, Immune and Gene therapy Lab , Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute , Stockholm , Sweden .|f Department of Immunology , School of Medicine, Bushehr University of Medical Sciences , Bushehr , Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hojjat-Farsangi
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D007155:Immunologic Factors; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000225:Adenine
keywords: Bruton’s tyrosine kinase; Ror1; ibrutinib; small-molecule Inhibitors; targeted cancer therapy; tyrosine kinases