Tumor microenvironment in head and neck squamous cell carcinomas: Predictive value and clinical relevance of hypoxic markers. A review

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Abstract
Background. Hypoxia and tumor cell proliferation are important factors determining the treatment response of squamous cell carcinomas of the head and neck. Successful approaches have been developed to counteract these resistance mechanisms although usually at the cost of increased short‐ and long‐term side effects. To provide the best attainable quality of life for individual patients and the head and neck cancer patient population as a whole, it is of increasing importance that tools be developed that allow a better selection of patients for these intensified treatments. Methods. A literature review was performed with special focus on the predictive value and clinical relevance of endogenous hypoxia‐related markers. Results. New methods for qualitative and quantitative assessment of functional microenvironmental parameters such as hypoxia, proliferation, and vasculature have identified several candidate markers for future use in predictive assays. Hypoxia‐related markers include hypoxia inducible factor (HIF)‐1α, carbonic anhydrase IX, glucose transporters, erythropoietin receptor, osteopontin, and others. Although several of these markers and combinations of markers are associated with treatment outcome, their clinical value as predictive factors remains to be established. Conclusions: A number of markers and marker profiles have emerged that may have potential as a predictive assay. Validation of these candidate assays requires testing in prospective trials comparing standard treatment against experimental treatments targeting the related microregional constituent. © 2007 Wiley Periodicals, Inc. Head Neck, 2007