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The Unfolded Protein Response and Integrated Stress Response to Anoxia

Authors' Affiliation: Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom

Requests for reprints: Adrian L. Harris, Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom. Phone: 44-1865226184; Fax: 44-1865226179; E-mail: aharris.lab{at}cancer.org.uk.

Abstract

The lack of oxygen delivery to tumor cells has profound consequences for tumor growth and correlates with poor prognosis. Some tumors contain regions of very severe hypoxia called anoxia, which constitutes a functionally different state to hypoxia. In response to anoxia, mammalian cells induce coordinated cytoprotective programs that are critical for tumor survival: the unfolded protein response and integrated stress response. Therefore, targeting additional components of anoxic pathways, besides the hypoxia-inducible response, may be effective for future anticancer therapies.

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