Caspase-mediated programmed cell death pathways as potential therapeutic targets in cancer

Cell Prolif. 2012 Jun;45(3):217-24. doi: 10.1111/j.1365-2184.2012.00814.x. Epub 2012 Mar 20.


The caspase family is well characterized as playing a crucial role in modulation of programmed cell death (PCD), which is a genetically regulated, evolutionarily conserved process with numerous links to many human diseases, most notably cancer. In this review, we focus on summarizing the intricate relationships between some members of the caspase family and their key apoptotic mediators, involving tumour necrosis factor receptors, the Bcl-2 family, cytochrome c, Apaf-1 and IAPs in cancer initiation and progression. We elucidate new emerging types of cross-talk between several caspases and autophagy-related genes (Atgs) in cancer. Moreover, we focus on presenting several PCD-modulating agents that may target caspases-3, -8 and -9, and their substrates PARP-1 and Beclin-1, which may help us harness caspase-modulated PCD pathways for future drug discovery.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis*
  • Apoptotic Protease-Activating Factor 1 / metabolism
  • Beclin-1
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cytochromes c / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Membrane Proteins / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / pathology
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Substrate Specificity


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Apoptotic Protease-Activating Factor 1
  • BECN1 protein, human
  • Beclin-1
  • Caspase Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Tumor Necrosis Factor
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • Caspases