Hypoxia-activated tumor pathways of angiogenesis and pH regulation independent of anemia in head-and-neck cancer.

Journal article

PURPOSE: Anemia is considered a major factor that counteracts the efficacy of radiotherapy, presumably because of reduced oxygen availability that leads to tumor hypoxia. Nevertheless, anemia is not the only factor defining oxygen availability, because a poor and/or immature vascular network may prevent blood flow and tumor oxygenation. Furthermore, the ability of tumors to upregulate hypoxia-regulated molecular pathways may affect radiosensitivity by mechanisms independent of the traditional concept of "oxygen effect." METHODS AND MATERIALS: In this study, we investigated whether the preoperative blood hemoglobin levels affect the activation status of hypoxia/angiogenic pathways (hypoxia inducible factors [HIF1 alpha and HIF2 alpha], carbonic anhydrase 9, differentiated embryo-chondrocyte protein, vascular endothelial growth factor, and microvessel density), in squamous cell head-and-neck cancer. RESULTS: Hypoxia/angiogenesis pathways were equally activated in tumors, independent of the patient's hemoglobin levels. The expression of HIF alphas was associated with microvessel density (p = 0.01). CONCLUSION: In the present study, we failed to show that a patient's anemia is a main contributor to the activation of hypoxia-regulated molecular pathways in squamous cell head-and-neck cancer. Impaired intratumoral blood flow or tumor-related gene/protein pathologic features may account for this finding. Targeting the hypoxia-regulated molecular cascade emerged as a complementary radiosensitization strategy for a large group of patients with hypoxic tumors, who are unlikely to benefit from conventional approaches aiming to improve intratumoral oxygen delivery through anemia correction.

Authors: Koukourakis, M; Giatromanolaki, A; Sivridis, E; Pastorek, J; Karapantzos, I

• Publication status: Published
• Journal: International journal of radiation oncology, biology, physics
• Volume: 59
• Issue: 1
• Pages: 67-71
• Publication date: 2004-05-01
• DOI: 10.1016/j.ijrobp.2003.10.016
• EISSN: 1879-355X
• ISSN: 0360-3016
• Language: English
• Keywords: Anemia; Carcinoma, Squamous Cell; Tumour and Angiogenesis Research Group; Hypoxia-Inducible Factor 1; DNA-Binding Proteins; Transcription Factors; Cell Hypoxia; Hydrogen-Ion Concentration; Carbonic Anhydrases; Head and Neck Neoplasms; Basic Helix-Loop-Helix Transcription Factors; Neoplasm Proteins; Hypoxia-Inducible Factor 1, alpha Subunit; Nuclear Proteins; Humans; Neovascularization, Pathologic; Hemoglobins; Proteins; Vascular Endothelial Growth Factor A