Pathology Oncology Research

, Volume 7, Issue 2, pp 95–106 | Cite as

Shared pathways: Death receptors and cytotoxic drugs in cancer therapy

  • Istvan Petak
  • Janet A. Houghton


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 stressinduced 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.


apoptosis tumor death receptor Fas drug p53 


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Copyright information

© Arányi Lajos Foundation 2001

Authors and Affiliations

  1. 1.Division of Experimental Hematology, Department of Hematology-OncologySt. Jude Children’s Research HospitalMemphisUSA

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