Hypoxia and cancer.
A major feature of solid tumours is hypoxia, decreased availability of oxygen, which increases patient treatment resistance and favours tumour progression. How hypoxic conditions are generated in tumour tissues and how cells respond to hypoxia are essential questions in understanding tumour progression and metastasis. Massive tumour-cell proliferation distances cells from the vasculature, leading to a deficiency in the local environment of blood carrying oxygen and nutrients. Such hypoxic conditions induce a molecular response, in both normal and neoplastic cells, that drives the activation of a key transcription factor; the hypoxia-inducible factor. This transcription factor regulates a large panel of genes that are exploited by tumour cells for survival, resistance to treatment and escape from a nutrient-deprived environment. Although now recognized as a major contributor to cancer progression and to treatment failure, the precise role of hypoxia signalling in cancer and in prognosis still needs to be further defined. It is hoped that a better understanding of the mechanisms implicated will lead to alternative and more efficient therapeutic approaches.
Brahimi-Horn
M Christiane
MC
Institute of Signaling, Developmental Biology and Cancer Research, University of Nice, CNRS UMR 6543, Centre A. Lacassagne, 33 Avenue Valombrose, 06189, Nice, France, brahimi@unice.fr
Chiche
Johanna
J
Pouysségur
Jacques
J
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death; D015687:Cell Hypoxia; D049109:Cell Proliferation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D051793:Hypoxia-Inducible Factor 1; D010100:Oxygen