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Venetoclax: Targeting BCL2 in Hematological Cancers

  • Annika Scheffold
  • Billy Michael Chelliah Jebaraj
  • Stephan Stilgenbauer
Chapter
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 212)

Abstract

Over the last years, targeted anti-cancer therapy with small-molecule inhibitors and antibodies moved to the forefront as a strategy to treat hematological cancers. These novel agents showed outstanding effects in treatment of patients, often irrespective of their underlying genetic features. However, evolution and selection of subclones with continuous treatment leads to disease relapse and resistance toward these novel drugs. Venetoclax (ABT-199) is a novel, orally bioavailable small-molecule inhibitor for selective targeting of B-cell lymphoma 2 (BCL2). Venetoclax is in clinical development and shows high efficacy and safety in particular in the treatment of chronic lymphocytic leukemia (CLL), but preliminarily also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The most important and impressive outcomes of venetoclax treatment include a rapid induction of apoptosis and drastic reduction of the tumor bulk within a few hours after administration. Venetoclax was approved by the FDA and EMA in 2016 for patients with previously treated CLL with del(17p13) and patients failing B cell receptor signaling inhibitors (EMA only), on the basis of a single-arm phase II trial demonstrating a tremendous response rate of 79% with complete remission in 20% of cases and an estimated 1-year progression-free survival of 72%. This review focuses on the mode of action, the preclinical models, and outcomes from various clinical trials with venetoclax in different hematologic cancers as well as future development.

Keywords

Venetoclax BCL2 inhibitors Hematologic cancer 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Annika Scheffold
    • 1
  • Billy Michael Chelliah Jebaraj
    • 1
  • Stephan Stilgenbauer
    • 1
  1. 1.Department of Internal Medicine IIIUlm UniversityUlmGermany

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