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Cancer Discov. 2017 Dec;7(12):1376-1393. doi: 10.1158/2159-8290.CD-17-0797. Epub 2017 Nov 16.

Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax.

Author information

1
AbbVie, Inc., North Chicago, Illinois. joel.leverson@abbvie.com.
2
Genentech, Inc., South San Francisco, California.
3
AbbVie, Inc., North Chicago, Illinois.
4
CRCINA, INSERM, CNRS, Université de Nantes, Université d'Angers, Nantes, France.
5
The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Dana-Farber Cancer Institute, Boston, Massachusetts.

Abstract

Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax. We review a number of preclinical studies that have deepened our understanding of BCL2 biology and facilitated the clinical development of venetoclax.Significance: Basic research into the pathways governing programmed cell death have paved the way for the discovery of apoptosis-inducing agents such as venetoclax, a BCL2-selective inhibitor that was recently approved by the FDA and the European Medicines Agency. Preclinical studies aimed at identifying BCL2-dependent tumor types have translated well into the clinic thus far and will likely continue to inform the clinical development of venetoclax and other BCL2 family inhibitors. Cancer Discov; 7(12); 1376-93. ©2017 AACR.

PMID:
29146569
PMCID:
PMC5728441
DOI:
10.1158/2159-8290.CD-17-0797
[Indexed for MEDLINE]
Free PMC Article

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