Hypoxia modulated gene expression: angiogenesis, metastasis and therapeutic exploitation

Tumour hypoxia is the result of an imbalance in oxygen supply and demand. I t is an adverse prognostic indicator in cancer as it modulates tumour progr ession and treatment. Many genes controlling tumour biology are oxygen regu lated, and new ones are constantly added to the growing list of hypoxia-ind uced genes. Of specific importance are hypoxia-responsive transcription fac tors, as they can modulate the expression of numerous different genes. Simi larly, growth factors which govern the formation of new blood vessels or wh ich control blood flow are vitally important for both the maintenance of th e primary tumour and metastases at distant sites. The purpose of this revie w is to present an update of selected issues regarding hypoxia-inducible ge ne expression and how this affects prognosis, angiogenesis and metastasis. It will conclude by discussing gene therapy as one possible means of exploi ting tumour hypoxia for the treatment of cancer. (C) 2000 Elsevier Science Ltd. All rights reserved.