Abstract

Hypoxia occurs in the majority of tumours, promoting angiogenesis, metastasis and resistance to therapy. Responses to hypoxia are orchestrated in part through activation of the hypoxia-inducible factor family of transcription factors (HIFs). Recently, two additional O₂-sensitive signalling pathways have also been implicated: signalling through the mammalian target of rapamycin (mTOR) kinase and signalling through activation of the unfolded protein response (UPR). Although they are activated independently, growing evidence suggests that HIF-, mTOR- and UPR-dependent responses to hypoxia act in an integrated way, influencing each other and common downstream pathways that affect gene expression, metabolism, cell survival, tumorigenesis and tumour growth.

Author affiliations

1. Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
2. Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
3. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
4. Selective Therapeutics Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
5. Maastricht Radiation Oncology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.

Correspondence to: Bradly G. Wouters^1,2,3,4,5 Email: bwouters@uhnresearch.ca

Published online 10 October 2008

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