Oncogenic Expression

• A complex network of intrinsic and extrinsic signaling pathways regulates apoptosis and determines whether a cell lives or dies.⁴
• Two main apoptotic pathways^1,2:
  • Extrinsic pathway: triggered through death receptors, such as the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor.
  • Intrinsic pathway: mediated by BCL-2 family members; also referred to as the mitochondrial pathway.
  • Both pathways converge to activate caspases, resulting in apoptosis.
• In most cancer cells, dysregulation of these pathways allows the cell to evade apoptosis.^1,4
• Dysregulated apoptotic pathways promote tumor development and metastasis, and confer resistance to conventional anticancer agents.^1,4

Therapeutic Potential

• The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy.^3,5
• Pharmacological research in this area focuses on approaches to restore the cancer cell's ability to die, including:
  • BCL-2 inhibition, which triggers the intrinsic pathway of apoptosis in certain cancers⁵
  • PARP inhibition, which inhibits salvage pathways for DNA repair³
  • TRAIL receptor activation, which triggers the extrinsic pathway of apoptosis in certain cancers⁵