Although hypoxia is not a new phenomenon, we now have a much greater understanding of the molecular links between hypoxic conditions and tumour development. Apart from driving angiogenesis, hypoxia also affects cellular metabolism, an area of significant interest in cancer research. A greater understanding of these closely related tumorigenic changes should prove fruitful in the pursuit of more effective cancer therapies.
Throughout 2008, Nature Reviews Cancer published a series of specially commissioned articles that examined the roles of hypoxia and metabolism in different aspects of tumour biology. The Collection presented here includes selected Reviews and Perspectives from that series, together with some recent Research Highlights on this topic. These articles and the accompanying library of the most relevant recent publications from Nature Research describe our current understanding of this field. The Collection articles are freely available until 23 April 2010, thanks to support from BioSpherix and Enzon.
From the editors
doi:10.1038/nrc2738
Research highlights
Metabolism: Giving antioxidants a bad rap
Sarah Seton-Rogers
doi:10.1038/nrc2742
Nature Reviews Cancer 9, 686-687 (2009)
Metabolism: Monitoring progression
Meera Swami
doi:10.1038/nrc2630
Nature Reviews Cancer 9, 229 (2009)
Metastasis: Oxidizing abnormalities
Gemma K. Alderton
doi:10.1038/nrc2624
Nature Reviews Cancer 9, 227 (2009)
Cancer stem cells: Survival skills
Sarah Seton-Rogers
doi:10.1038/nrc2614
Nature Reviews Cancer 9, 147 (2009)
Reviews
Hypoxia signalling through mTOR and the unfolded protein response in cancer
Bradly G. Wouters & Marianne Koritzinsky
doi:10.1038/nrc2501
Nature Reviews Cancer 8, 851-864 (2008)
Responses to hypoxia are orchestrated not only through activation of the hypoxia–inducible factor family of transcription factors (HIFs), but also through HIF–independent signalling pathways. How are these pathways integrated?
The von Hippel–Lindau tumour suppressor protein: O2 sensing and cancer
William G. Kaelin Jr
doi:10.1038/nrc2502
Nature Reviews Cancer 8, 865-873 (2008)
Deregulation of hypoxia-inducible factor (HIF) is an established feature of tumours that develop in patients with von Hippel–Lindau disease, caused by inactivating germline mutations of the VHL tumour suppressor gene. However, HIF-independent activities of VHL also seem to be important for the pathogenesis of the disease.
Perspectives
The interplay between MYC and HIF in cancer
Chi V. Dang, Jung-whan Kim, Ping Gao & Jason Yustein
doi:10.1038/nrc2274
Nature Reviews Cancer 8, 51-56 (2008)
This Perspective considers the differences between the hypoxia-inducible factor (HIF)–MYC transcriptional network that operates under normal homeostatic conditions and the network that operates in a tumorigenic milieu.
The impact of O2 availability on human cancer
Jessica A. Bertout, Shetal A. Patel & M. Celeste Simon
doi:10.1038/nrc2540
Nature Reviews Cancer 8, 967-975 (2008)
During the past century, the response to hypoxia has emerged as an important phenotypic determinant of a tumour, with repercussions for sensitivity to radiation and chemotherapy. This Timeline provides a historical overview of responses to hypoxia while looking forward to therapeutic strategies that are being developed to exploit them.