title: The role of caspase-8 in resistance to cancer chemotherapy.
abstract: Toxicity of chemotherapeutic agents against cancer cells is mediated through the initiation of programmed cell death. Apoptosis is an evolutionarily conserved cascade of intracellular proteolytic events propagated by a family of cysteine proteases called caspases. Many receptor- and non-receptor-mediated death signals induce apoptosis via activation of caspase-8 (FLICE/MACH). Mechanisms of tumor resistance to cytotoxic drugs through decreased apoptosis may occur by altered expression of caspase-8, upregulation of caspase-8 inhibitors like FLIP (FLICE-like Inhibitory Protein), or sequestration of caspase-8 by Bcl-2. Modulation of caspase-8 and apoptosis may be a therapeutic strategy for sensitization of drug-resistant malignancies to radiation or combination chemotherapy.
authors: Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors: P K
authors: PK
authors: Kim
authors: R
authors: R
authors: Mahidhara
authors: D W
authors: DW
authors: Seol
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases