BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines.

2018-12-10

Merino, Delphine

Kelly, Gemma L

Lessene, Guillaume

Wei, Andrew H

Roberts, Andrew W

Strasser, Andreas

BCL-2

BH3-mimetic drugs

BH3-only proteins

MCL-1

apoptosis

cancer

Journal Article

10.1016/j.ccell.2018.11.004

Defects in apoptotic cell death can promote cancer and impair responses of malignant cells to anti-cancer therapy. Pro-survival BCL-2 proteins prevent apoptosis by keeping the cell death effectors, BAX and BAK, in check. The BH3-only proteins initiate apoptosis by neutralizing the pro-survival BCL-2 proteins. Structural analysis and medicinal chemistry led to the development of small-molecule drugs that mimic the function of the BH3-only proteins to kill cancer cells. The BCL-2 inhibitor venetoclax has been approved for treatment of refractory chronic lymphocytic leukemia and this drug and inhibitors of pro-survival MCL-1 and BCL-XL are being tested in diverse malignancies.

link

Cancer cell 2018; 34(6): 879-891

Cancer cell