Review
Nature Reviews Drug Discovery 7, 1001-1012 (December 2008) | doi:10.1038/nrd2637
Focus on: Apoptosis
Directing cancer cells to self-destruct with pro-apoptotic receptor agonists
Avi Ashkenazi1 About the author
Abstract
Each day, the human body eliminates billions of unwanted cells by apoptotic suicide. Apoptosis provides an important barrier against cancer; however, specific mutations enable some tumour cells to escape apoptotic death and become more malignant. Two signalling pathways initiate apoptosis: one acts through intracellular Bcl-2 proteins, the other through cell-surface pro-apoptotic receptors. New molecular insights have inspired the development of pro-apoptotic receptor agonists (PARAs), including the recombinant human protein apoptosis ligand 2/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) and agonistic monoclonal antibodies to its signalling receptors. Acting alone, or in concert with other agents, PARAs may overcome key apoptosis blocks and direct cancer cells to self-destruct.
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Author affiliations
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Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080-4918, USA.
Email: aa@gene.com
Published online 7 November 2008
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