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

Head Neck. 2007 Jun;29(6):591-604. doi: 10.1002/hed.20543.

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)-1alpha, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia / physiopathology
  • Animals
  • Biomarkers, Tumor / metabolism*
  • Carbonic Anhydrases / metabolism
  • Carcinoma, Squamous Cell / blood supply*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Hypoxia / physiology
  • Cell Proliferation
  • Diagnostic Imaging
  • Glucose Transport Proteins, Facilitative / metabolism
  • Head and Neck Neoplasms / blood supply*
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Hemoglobins / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Polarography
  • Receptors, Erythropoietin / metabolism

Substances

  • Biomarkers, Tumor
  • Glucose Transport Proteins, Facilitative
  • Hemoglobins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Receptors, Erythropoietin
  • Carbonic Anhydrases