Literature DB >> 27695617

The potential of venetoclax (ABT-199) in chronic lymphocytic leukemia.

Gilad Itchaki1, Jennifer R Brown2.   

Abstract

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.

Entities:  

Keywords:  ABT-199; B-cell chronic lymphocytic leukemia; venetoclax

Year:  2016        PMID： 27695617      PMCID： PMC5026291          DOI： 10.1177/2040620716655350

Source DB:  PubMed          Journal:  Ther Adv Hematol        ISSN： 2040-6207


  69 in total

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9.  Cyclin E/Cdk2-dependent phosphorylation of Mcl-1 determines its stability and cellular sensitivity to BH3 mimetics.

Authors:  Gaurav S Choudhary; Trinh T Tat; Saurav Misra; Brian T Hill; Mitchell R Smith; Alexandru Almasan; Suparna Mazumder
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10.  Loss in MCL-1 function sensitizes non-Hodgkin's lymphoma cell lines to the BCL-2-selective inhibitor venetoclax (ABT-199).

Authors:  D C Phillips; Y Xiao; L T Lam; E Litvinovich; L Roberts-Rapp; A J Souers; J D Leverson
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7.  Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition.

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