Clinical potential of targeting Bruton's tyrosine kinase.
Targeting Bruton's tyrosine kinase (BTK) with a small-molecule inhibitor may be useful in treatment of BTK-expressing malignancies because of the antiapoptotic function of BTK in cancer cells. Furthermore, BTK inhibitors also exhibit antithrombotic properties, which may be desirable in the context of the increased risk of thromboembolic complications in cancer patients. This review will focus on the role of BTK in drug resistance in cancer, thromboembolism, and various pathologic immune responses, such as graft-versus-host disease. The therapeutic potential of targeting BTK is illustrated by discussion of the biologic activity profile of the rationally designed BTK inhibitor LFM-A13.
Uckun
Fatih M
FM
Parker Hughes Cancer Center, Roseville, Minnesota 55113, USA.
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000577:Amides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015195:Drug Design; D006086:Graft vs Host Disease / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009570:Nitriles / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D013923:Thromboembolism / Q000188:drug therapy / Q000201:enzymology
D000577:Amides; C118451:LFM A13; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human