Targeting hypoxia to overcome radiation resistance in head & neck cancers: real challenge or clinical fairytale?

ABSTRACT

Introduction: Tumor hypoxia is a major cause for failure of therapy in patients with inoperable head and neck cancers.

Areas covered: Various anti-hypoxic treatment strategies (e.g. hyperbaric oxygenation, hypoxic cell sensitizers) have been tested in clinical trials in head and neck cancer over the past 30 years and have shown modest improvements in combination with radiotherapy in meta-analyses. Anemia worsens tumor hypoxia, but anemia correction had no significant effect. New approaches (e.g. anti-HIF-directed molecular therapies) have just entered early clinical studies and data are lacking.

Expert commentary: A new attractive and promising approach derives from recent advances in imaging and radiotherapy delivery. Progress in imaging of hypoxia (e.g. by positron emission tomography) can select patients for specific therapies and may, in particular, facilitate anti-hypoxia-directed radiotherapy which has become feasible with advanced radiotherapy techniques (IMRT with ‘dose-painting’). The combination of both methods may offer a powerful tool for effective targeting of hypoxia in the near future.

KEYWORDS:

• Head and neck cancers
• radiotherapy
• hypoxia
• prognosis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Notes

1. Within malignant tumors, only a part of the malignant cells have the capability of unlimited self-renewal. This cell fraction has been addressed as ‘clonogenic fraction’ or clonogenic cells in the older radiobiological literature. These cells share various properties with normal stem cells and are nowadays mostly called tumor stem cells. We personally prefer the term ‘clonogenic’ because unlimited viability and reproducibility is the main feature of clonogenic tumor cells. A main characteristic of stem cells in normal tissue, namely the reprograming and pluripotency with directed development of clearly defined cell lines, however, is lacking in tumors.