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Targeting apoptosis: selected anticancer strategies

Nature Reviews Drug Discovery volume 7, pages 971–972 (2008)Cite this article

Apoptosis pathways

The two apoptosis pathways of interest are the extrinsic pathway and the intrinsic pathway. The extrinsic pathway operates through cell-surface death receptors (DRs), and the intrinsic pathway is tightly controlled by the BCL-2 family of proteins and involves the disruption of mitochondrial membrane integrity in response to cellular insults or other danger signals. Both pathways converge at the level of the effector caspases — proteolytic enzymes that carry out the cell death response. These two pathways sit within a broader superstructure of other signalling pathways and molecular targets with links to apoptosis, such as p53–MDM2 and NF-κB. The two areas that are most likely to produce approved products in the near future are agents that promote apoptosis via the BCL-2 family of regulatory proteins, or by acting as pro-apoptotic receptor agonists (PARAs). A third area of great interest is adjuvant strategies that target interfaces between the extrinsic and intrinsic apoptosis pathways.

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Figure 1: Leading indications for mid/late clinical development.
Figure 2: Aggregate sales potential of PARA agents in the major pharmaceutical markets (US, France, Germany, Italy, Spain, UK and Japan) in $US billions.

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Authors and Affiliations

  1. Shane Storey is a senior biotechnology and healthcare analyst with Wilson HTM Investment Group, Level 38, 71 Eagle Street, Brisbane, Queensland 4000, Australia. shane.storey@wilsonhtm.com.au,

    Shane Storey

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Storey, S. Targeting apoptosis: selected anticancer strategies. Nat Rev Drug Discov 7, 971–972 (2008). https://doi.org/10.1038/nrd2662

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