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: Maria Eugenia Guicciardi, Gregory J Gores
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 123 Issue 9 Pg. 3706-8 (Sep 2013) ISSN: 1558-8238 [Electronic] United States
• PMID: 23979156 (Publication Type: Journal Article, Comment)

Chemical References

• Antineoplastic Agents
• X-Linked Inhibitor of Apoptosis Protein
• XIAP protein, human
• CASP3 protein, human
• CASP7 protein, human
• Caspase 3
• Caspase 7
• Lysine

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Caspase 3 (deficiency)
• Caspase 7 (metabolism)
• Drug Resistance, Neoplasm
• Female
• Humans
• Lysine (analogs & derivatives, pharmacology)
• X-Linked Inhibitor of Apoptosis Protein (metabolism)