title: Tumor microenvironment in head and neck squamous cell carcinomas: predictive value and clinical relevance of hypoxic markers. A review.
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.
authors.affiliation: Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, The Netherlands.
authors.forename: Ilse J
authors.initials: IJ
authors.lastname: Hoogsteen
authors.forename: Henri A M
authors.initials: HA
authors.lastname: Marres
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
authors.forename: Albert J
authors.initials: AJ
authors.lastname: van der Kogel
authors.forename: Johannes H A M
authors.initials: JH
authors.lastname: Kaanders
mesh_terms: D000740:Anemia / Q000503:physiopathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D049109:Cell Proliferation; D003952:Diagnostic Imaging; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D011048:Polarography; D017467:Receptors, Erythropoietin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D051246:Glucose Transport Proteins, Facilitative; D006454:Hemoglobins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017467:Receptors, Erythropoietin; D002256:Carbonic Anhydrases