Unleashing Blocked Apoptosis in Cancer Cells: New MCL1 Inhibitors Find Their Groove

Unleashing blocked apoptosis has emerged as an important tool in treating cancer as shown by the recent success of the BCL2 inhibitor venetoclax. However, MCL1 represents another important target as it is the predominant survival signal in many types of cancers and functions as a resistance mechanism to BCL2 inhibition. Caenepeel and colleagues and Ramsey and colleagues have developed two novel, potent, and selective MCL1 inhibitors that are effective against many hematologic malignancies, and Nangia and colleagues describe how one of these inhibitors can be successfully combined with BCL-xL and MEK inhibition to treat KRAS-mutated lung cancer.See related article by Ramsey et al., p. 1566.See related article by Caenepeel et al., p. 1582.See related article by Nangia et al., p. 1598.