Shared pathways: death receptors and cytotoxic drugs in cancer therapy

Pathol Oncol Res. 2001;7(2):95-106. doi: 10.1007/BF03032574.


Death ligands (TNF, FasL, TRAIL) and their respective death receptor signaling pathways can be used to induce tumor cells to undergo apoptosis. Chemotherapeutic drugs can induce apoptosis and the upregulation of death ligands or their receptors. Downstream events following cytotoxic stress-induced DNA damage and the signaling pathways that lead to the induction of apoptosis may be either dependent or independent of death receptor signaling. The involvement of the Fas signaling pathway in chemotherapy-induced apoptosis has been the most extensively studied, with the current emergence of information on the TRAIL signaling pathway. Fas-mediated and chemotherapy-induced apoptosis can converge at the level of the receptor, FasL, DISC formation, activation of the initiator caspase-8, at the level of the mitochondria, or at the level of downstream effector caspase activation. Convergence is influenced by the specific form of DNA damage, the cellular environment, and the specific pathway(s) by which death receptor-mediated or drug-mediated apoptosis are induced. This review discusses the different levels of interaction between signaling pathways in the different forms of cell death.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins
  • Caspases / metabolism
  • Ceramides / physiology
  • DNA Damage
  • Enzyme Activation / drug effects
  • Fas Ligand Protein
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Membrane Glycoproteins / physiology*
  • Mitochondria / drug effects
  • Mitogen-Activated Protein Kinases / physiology
  • Models, Biological
  • NF-kappa B / physiology
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Receptors, Tumor Necrosis Factor / drug effects
  • Receptors, Tumor Necrosis Factor / physiology*
  • Signal Transduction / drug effects
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / physiology*
  • fas Receptor / physiology*


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Ceramides
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Mitogen-Activated Protein Kinases
  • Caspases