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Pharmacyclics, Inc. Message Board

  • popeyethesailor61 popeyethesailor61 Oct 10, 2013 11:56 PM Flag

    two targets formthe price of one

    As shown in the article by Dubovsky et al,1 the small molecule ibrutinib, which inhibits BTK signaling and suppresses malignant B-cell growth, also inhibits ITK and thereby skews the development of T cells toward a Th1 phenotype. The authors show in neoplastic mouse models, including a mouse model of CLL and parasitic infection models using Leishmania major and infectious disease models using Listeria monocytogenes, that ibrutinib is able to specifically promote Th1 responses, resulting in improved outcomes. These findings strongly suggest a pleiotropic mechanism of action of ibrutinib. Not only is there a specific inhibition and downregulation of BCR signaling directly inhibiting the proliferation and survival of the malignant B cell, there is also inhibition of ITK with a dramatic change in the tumor microenvironment promoting a Th1 response that promotes immune regulation that inhibits malignant cell growth (see figure). The findings of this study suggest that ibrutinib may be successful in the treatment of a variety of diseases, particularly B-cell malignancies, because of its effect not only on the malignant B cell and on the immune response and tumor microenvironment.

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