Abstract

During the past century it has been established that regions within solid tumours experience mild to severe O₂ deprivation owing to aberrant vascular function. These hypoxic regions are associated with altered cellular metabolism, as well as increased resistance to radiation and chemotherapy. As discussed in this Timeline, over the past decade work from many laboratories has elucidated the mechanisms by which hypoxia-inducible factors (HIFs) modulate tumour cell metabolism, angiogenesis, growth and metastasis. The central role played by intra-tumoural hypoxia and HIF in these processes has made them attractive therapeutic targets in the treatment of multiple human malignancies.

Author affiliations

1. Jessica A. Bertout, Shetal A. Patel and M. Celeste Simon are at the Abramson Family Cancer Research Institute, Jessica A. Bertout is also at the School of Veterinary Medicine, Shetal A. Patel, and M. Celeste Simon are at the School of Medicine, and M. Celeste Simon is at the Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Correspondence to: M. Celeste Simon¹ Email: celeste2@mail.med.upenn.edu

Published online 6 November 2008

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