Sign up for Table of Contents Alerts.
Email this page
Print this page
Review
Tumor Microenvironment and the Response to Anticancer Therapy
J. Martin Brown
volume 1 | issue 5
September/October 2002Pages: 453-458
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
Human solid tumors are invariably less well oxygenated than normal tissues. This leads to resistance to radiotherapy and anticancer chemotherapy, as well as predisposing for increased tumor metastases. Prolonged hypoxia of the tumor tissue also leads to necrosis, and necrotic regions are also characteristic of solid tumors. These two characteristics—hypoxia and necrosis—represent clear differences between tumors and normal tissues and are potentially exploitable in cancer treatment. This review focuses on the phenomenon of tumor hypoxia and how hypoxia and its accompanying necrosis can be exploited in therapy. One such strategy is to use drugs that are toxic only under hypoxic conditions, and the first drug of this class to enter clinical testing, tirapazamine, is showing considerable promise. The second way to exploit hypoxia is to take advantage of the selective induction under hypoxia of the transcription factor HIF-1 (hypoxia-inducible factor 1). Gene therapy strategies based on this are in development. Finally, tumor hypoxia can be exploited using live obligate anaerobes that have been genetically engineered to express enzymes that can activate non-toxic prodrugs into toxic chemotherapeutic agents.
Key Words:
Tumor hypoxia, Acute hypoxia, Chronic hypoxia, Tirapazamine, Gene therapy, Clostridia, HIF-1
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.