While targeting Bcl-2 holds promise, several challenges remain. Cancer cells may develop resistance to Bcl-2 inhibitors, often through the overexpression of other anti-apoptotic proteins such as Mcl-1 or Bcl-xL. Additionally, the toxicity associated with Bcl-2 inhibitors, particularly in normal cells that rely on Bcl-2 for survival, can pose significant side effects. Therefore, combination therapies that target multiple pathways are being explored to overcome resistance and minimize toxicity.
