Directing Cancer Cells to Self-Destruct With Pro-Apoptotic Receptor Agonists

Nat Rev Drug Discov. 2008 Dec;7(12):1001-12. doi: 10.1038/nrd2637. Epub 2008 Nov 7.

Abstract

Each day, the human body eliminates billions of unwanted cells by apoptotic suicide. Apoptosis provides an important barrier against cancer; however, specific mutations enable some tumour cells to escape apoptotic death and become more malignant. Two signalling pathways initiate apoptosis: one acts through intracellular Bcl-2 proteins, the other through cell-surface pro-apoptotic receptors. New molecular insights have inspired the development of pro-apoptotic receptor agonists (PARAs), including the recombinant human protein apoptosis ligand 2/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) and agonistic monoclonal antibodies to its signalling receptors. Acting alone, or in concert with other agents, PARAs may overcome key apoptosis blocks and direct cancer cells to self-destruct.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / drug effects*
  • Cell Transformation, Neoplastic / drug effects
  • DNA, Neoplasm / drug effects
  • DNA, Neoplasm / genetics
  • Drug Design
  • Fas-Associated Death Domain Protein / drug effects
  • Fas-Associated Death Domain Protein / physiology
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Receptors, Death Domain / drug effects
  • Receptors, Death Domain / physiology
  • Signal Transduction / physiology

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • DNA, Neoplasm
  • Fas-Associated Death Domain Protein
  • Receptors, Death Domain