Discovery, development and application of drugs targeting BCL-2 pro-survival proteins in cancer

Author:

Lee Erinna F.123,Fairlie W. Douglas123ORCID

Affiliation:

1. La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia

2. Cell Death and Survival Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria 3084, Australia

3. School of Cancer Medicine, La Trobe University, Bundoora, Victoria 3086, Australia

Abstract

The discovery of a new class of small molecule compounds that target the BCL-2 family of anti-apoptotic proteins is one of the great success stories of basic science leading to translational outcomes in the last 30 years. The eponymous BCL-2 protein was identified over 30 years ago due to its association with cancer. However, it was the unveiling of the biochemistry and structural biology behind it and its close relatives’ mechanism(s)-of-action that provided the inspiration for what are now known as ‘BH3-mimetics’, the first clinically approved drugs designed to specifically inhibit protein–protein interactions. Herein, we chart the history of how these drugs were discovered, their evolution and application in cancer treatment.

Publisher

Portland Press Ltd.

Subject

Biochemistry

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