Toward targeting antiapoptotic MCL-1 for cancer therapy
- Author(s)
- Kelly, GL; Strasser, A;
- Journal Title
- Annual Review of Cancer Biology
- Publication Type
- Journal Article
- Abstract
- Apoptosis is critical for embryonic development, tissue homeostasis, and the removal of infected or otherwise dangerous cells. It is controlled by three subgroups of the BCL-2 protein family-the BH3-only proteins that initiate cell death; the effectors of cell killing, BAX and BAK; and the antiapoptotic guardians, including MCL-1 and BCL-2. Defects in apoptosis can promote tumorigenesis and render malignant cells refractory to anticancer therapeutics. Activation of cell death by inhibiting antiapoptotic BCL-2 family members has emerged as an attractive strategy for cancer therapy, with the BCL-2 inhibitor venetoclax leading the way. Large-scale cancer genome analyses have revealed frequent amplification of the locus encoding antiapoptotic MCL-1 in human cancers, and functional studies have shown that MCL-1 is essential for the sustained survival and expansion of many types of tumor cells. Structural analysis and medicinal chemistry have led to the development of three distinct small-molecule inhibitors of MCL-1 that are currently undergoing clinical testing. Copyright © 2020 by Annual Reviews.
- Publisher
- Annual Reviews
- Research Division(s)
- Blood Cells And Blood Cancer
- Publisher's Version
- https://doi.org/10.1146/annurev-cancerbio-030419-033510
- Open Access at Publisher's Site
https://doi.org/110.1146/annurev-cancerbio-030419-033510- NHMRC Grants
- NHMRC/1086291, NHMRC/1020363,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-05-18 11:15:15
Last Modified: 2020-05-19 09:13:00