Directing cancer cells to self-destruct with pro-apoptotic receptor agonists

A Ashkenazi - Nature reviews Drug discovery, 2008 - nature.com
Nature reviews Drug discovery, 2008nature.com
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 …
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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