Open AccessThe potential of venetoclax (ABT-199) in chronic lymphocytic leukemia
Author(s) -
Gilad Itchaki,
Jennifer R. Brown
Publication year - 2016
Publication title -
therapeutic advances in hematology
Language(s) - English
Resource type - Journals
eISSN - 2040-6215
pISSN - 2040-6207
DOI - 10.1177/2040620716655350
Subject(s) - venetoclax , chronic lymphocytic leukemia , medicine , ven , leukemia , mechanism (biology) , cancer research , cd52 , lymphoma , immunology , apoptosis , ibrutinib , alemtuzumab , antibody , biology , genetics , computer science , computer security , epistemology , philosophy
Venetoclax (VEN, ABT-199/GDC-0199) is an orally bioavailable BH3-mimetic that specifically inhibits the anti-apoptotic B-cell lymphoma/leukemia 2 (BCL2) protein. Although BCL2 overexpression is not genetically driven in chronic lymphocytic leukemia (CLL), it is nearly universal and represents a highly important and prevalent mechanism of apoptosis evasion, making it an attractive therapeutic target. This review summarizes the role of BCL2 in CLL pathogenesis, the development path targeting its inhibition prior to VEN, and the preclinical and clinical data regarding the effectiveness and safety of VEN. We further strive to contextualize VEN in the current CLL treatment landscape and discuss potential mechanisms of resistance.
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