Causes, Detection and Characterization of Tumor Hypoxia

Abstract

Tumor oxygenation is heterogeneous and severely compromised as compared to normal tissue. Hypoxia, i.e., oxygen depletion as a consequence of an imbalance between oxygen supply and cellular oxygen consumption, mostly results from inadequate perfusion and diffusion within tumors and from reduced O₂ transport capacity in anemic patients. Detection of tumor hypoxia has been performed using minimally invasive approaches, imaging PET and MRI techniques and immunohistochemistry on tissue biopsies. The development of tumor hypoxia is independent of a series of relevant tumor characteristics (e.g., clinical size, stage, histology, and grade) and various patient demographics. Overall median pO₂ in cancers of the uterine cervix, head and neck, and breast is about 10 mmHg with the overall hypoxic fraction (pO₂ ≤ 2.5 mmHg) being approx. 25%. Metastatic lesions do not substantially deviate from the oxygenation status of (their) primary tumors. Identification of tumor hypoxia may allow an assessment of a tumor’s potential to develop an aggressive phenotype or acquired treatment resistance, both of which lead to poor prognosis. Detection of hypoxia in the clinical setting may therefore be helpful in selecting high-risk patients for individual and/or more intensive treatment schedules.