What is a BCL-2 inhibitor and when is it used?

What is a BCL2 inhibitor and when is it used? BCL2 inhibitor like Vananaclax is a drug that inhibits a mechanism which causes leukemia and other cancer cells to survive chemotherapy. What happens is typically when the cell gets signals to induce cell death, they go ahead and apoptose or undergo programmed death and they die. What happens is over expression of the BCL2 protein allows cells to resist those death signals and to not die and is a primary cause of resistance in leukemia cells. AML cells have high levels of BCL2, leukemic stem cells do as well. So by targeting BCL2 we're rendering the drug much less able to withstand additional therapy. Vananaclax as a single agent doesn't work very well but when you combine it with another drug that's inducing that cell death signal and in this case we are using azacytidine, we suddenly see an enhancement of activity. Vananaclax and azacytidine for older newly diagnosed patients results in a 66% overall response rate whereas the standard of care azacytidine alone was really less than 20%. But again it has to be given in combination, it's a pill, it does cause a lot of decreased blood counts, patients getting that combo need to be monitored but it's really been a game changer in our ability to treat AML.