title: Unshackling caspase-7 for cancer therapy.
abstract: Numerous solid tumors and hematologic malignancies acquire resistance to apoptosis-inducing chemotherapeutic drugs by downregulating the key effector caspase-3. These cells rely on caspase-7 to execute the apoptotic program, yet binding with XIAP constitutively inhibits active caspase-7 (p19/p12-CASP7). In this issue, Lin et al. describe how a newly synthesized drug is able to disrupt the XIAP:p19/p12-CASP7 complex and induce apoptosis in caspase-3-deficient cancer cells in vitro and in vivo. As this compound appears to exhibit minimal toxicity on normal tissues, it may represent a promising therapeutic agent to help treat caspase-3-deficient tumors.
authors: Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors: Maria Eugenia
authors: ME
authors: Guicciardi
authors: Gregory J
authors: GJ
authors: Gores
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000172:deficiency*; D053179:Caspase 7 / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D008239:Lysine
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