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Shared pathways: Death receptors and cytotoxic drugs in cancer therapy

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  • Published:
Pathology Oncology Research

Abstract

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.

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Authors and Affiliations

  1. Division of Experimental Hematology, Department of Hematology-Oncology, St. Jude Children’s Research Hospital, 332 North Lauderdale, 38105, Memphis, TN, USA

    Istvan Petak & Janet A. Houghton

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  1. Istvan Petak
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  2. Janet A. Houghton
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Correspondence to Janet A. Houghton.

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This research was supported by NIH Awards RO1 CA 32613, the Cancer Center Support (CORE) Grant CA 21765, and by the American Lebanese Syrian Associated Charities. I. Petak was supported in part by a scholarship from the Fulbright Program, and by the 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

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Petak, I., Houghton, J.A. Shared pathways: Death receptors and cytotoxic drugs in cancer therapy. Pathol. Oncol. Res. 7, 95–106 (2001). https://doi.org/10.1007/BF03032574

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