A compound that activates cell death pathways via a new mechanism is reported this week in Nature Chemical Biology.
The Bcl-2 family of proteins forms a complex protein-protein interaction network that can either promote or counter cell death, depending on the activation state of the different members. In cancer cells, the balance of activity from this network is often disrupted to promote cancer cell survival. Anti-cancer strategies targeting this family have largely aimed to inhibit the activity of family members that promote cell survival. The activation of one protein in this family called Bax can be sufficient to activate cell death pathways.
Loren Walensky and colleagues report BAM7, a small molecule that can selectively activate Bax in cells by triggering a conformational change in the protein and that promotes cell death. Because both normal and cancer cells express Bax, it remains to be seen whether this strategy can be effective in anti-cancer treatment, but the discovery and validation of BAM7 as a selective activator of Bax represents a new approach to killing cancer cells.