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The Inhibitor of Apoptosis Proteins as Therapeutic Targets in Cancer

Authors' Affiliation: Department of Protein Engineering, Genentech, Inc., South San Francisco, California

Requests for reprints: Wayne J. Fairbrother, Department of Protein Engineering, Genentech, Inc., South San Francisco, CA 94080. Phone: 650-225-6372; Fax: 650-225-3734; E-mail: fairbro{at}gene.com.

Abstract

Apoptosis is a cell suicide process with a major role in development and homeostasis in vertebrates and invertebrates. Inhibition of apoptosis enhances the survival of cancer cells and facilitates their escape from immune surveillance and cytotoxic therapies. Among the principal molecules contributing to this phenomenon are the inhibitor of apoptosis (IAP) proteins, a family of antiapoptotic regulators that block cell death in response to diverse stimuli through interactions with inducers and effectors of apoptosis. IAP proteins are expressed in the majority of human malignancies at elevated levels and play an active role in promoting tumor maintenance through the inhibition of cellular death and participation in signaling pathways associated with malignancies. Here, we discuss the role of IAP proteins in cancer and options for targeting IAP proteins for therapeutic intervention.

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