BCL-2 family deregulation in colorectal cancer: potential for BH3 mimetics in therapy

We further review BH3 mimetics as a therapeutic opportunity to target this pathway and evaluate their potential for colorectal cancer treatment

Prashanthi Ramesh; Jan Paul Medema


Scholarcy highlights

  • Programmed cell death is an essential process regulating tissue homeostasis and stress response in many organisms
  • In this review we focus on the role of the BCL-2 family of proteins in cancer and on the intrinsic or mitochondrial pathway of apoptosis, which is regulated by this family
  • Knocking out BCL-W does not affect spontaneous intestinal apoptosis. These KO mice do display an important role for BCL-W in damage-induced apoptosis, in the small intestine. Both spontaneous and damageinduced apoptosis are unaffected by BAK molecules exist as inactive monomers KO, while the colon in BAK-null mice is significantly affected with crypt hyperplasia and reduced damage-induced apoptosis [111, Table 1 Expression alterations of BCL-2 family members in colorectal cancer progression from adenoma-to-carcinoma compared to healthy epithelium
  • Recent findings have provided novel insights into the interactions of the BCL-2 family members that regulate the intrinsic pathway of apoptosis
  • De-regulation of the BCL-2 family occurs through various mechanisms and many CRC tumors show dependence on different anti-apoptotic proteins through different stages of the disease, making them a promising target for therapy
  • Implementing strategies to reduce the toxicities associated with these inhibitors and determining the appropriate BH3 mimetic to administer in a context-dependent and personalized manner could help untap the full potential of these novel inhibitors in CRC treatment

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