What Are the Challenges in Targeting Bcl-2 Family Proteins?
Despite the potential, there are several challenges in targeting Bcl-2 family proteins: 1. Resistance Mechanisms: Cancer cells can develop resistance to BH3 mimetics through various mechanisms, such as mutations in the target proteins or upregulation of other anti-apoptotic proteins. 2. Toxicity: Given the critical role of Bcl-2 family proteins in normal cell survival, targeting these proteins can lead to toxicities in normal tissues, particularly in organs with high turnover rates like the gastrointestinal tract. 3. Redundancy: The presence of multiple anti-apoptotic proteins can create redundancy, making it difficult to achieve complete inhibition of the survival pathways.
