Oxygenation Status of Malignant Tumors vs. Normal Tissues: Critical Evaluation and Updated Data Source Based on Direct Measurements with pO2 Microsensors

Abstract

AbstractImmature and chaotic vascular networks with critically increased intervascular distances are characteristic features of malignant tumors. Spatial and temporal heterogeneities of blood flow and associated availabilities of O2, together with limited diffusive O2 transport, and -in some patients- anemia, obligatorily lead to tumor hypoxia (= critically reduced O2 levels) on macro- and microscopic scales. This detrimental condition, recently classified as a key hallmark of malignant growth, acts (a) as a barrier in most antitumor treatments, and (b) leads to malignant progression based on hypoxia-induced changes of the genome, transcriptome, and proteome, and finally to poor patient survival. This knowledge is, to a great extent, based on the systematic detection of tumor hypoxia in the clinical setting since the late 1980s. Precise assessment of the tumor oxygenation status was made possible using minimally invasive polarographic pO2 microsensors in a series of research projects. To assess tumor hypoxia in the clinical setting, it is highly desirable to use technologies with (a) high spatial and temporal resolutions, (b) the capability to judge the severity of tumor hypoxia, (c) to allow mapping of pO2 of the whole tumor mass, and (d) to enable serial investigations in order to verify treatment-related changes in tumor hypoxia. Selection and treatment of cancer patients according to their individual tumor oxygenation/hypoxia status for intensified and/or personalized hypoxia-targeted treatment strategies should be the ultimate goal.