Focus on tumor oxygen consumption : development of methods to measure oxygen consumption and evaluation of innovative co-treatment for radiotherapy
(2010)
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- (en) Response to cancer treatment is largely influenced by the tumor microenvironment. One of the most important factors playing a crucial role in this process is the existence of hypoxia in solid tumors. It has been shown to decrease the therapeutic efficacy of radiation treatment, surgery and some forms of chemotherapy. Several studies have shown improved outcomes for cancer patients whose tumors have lower hypoxic fractions. Tumor hypoxia also promotes metastasis, selects cells with malignant phenotypes, and promotes angiogenesis. Since inadequate tumor oxygenation is a considerable obstacle in the successful therapy of some human tumors, one relevant approach is the improvement of the O2 status of hypoxic tumors or hypoxic areas during cytotoxic therapies. A number of strategies to improve tumor oxygenation and increase its uniformity have been considered. These include enhancing O2 availability and/or reducing cellular respiration rate, parameters that crucially determine the O2 status of a given tissue. Tumor oxygenation is a matter of supply and demand of the respiring cancer cells. However, modulation of O2 consumption seems to be a much more efficient way of affecting the oxygenation status than modification of the O2 availability through elevating blood flow. Several pharmacological drugs that inhibit cellular oxygen consumption have been characterized for their potential to increase tumor oxygenation and thereby enhance radiosensitivity. In view of its clinical importance, several techniques have been developed to measure oxygenation status in tissues and tumors in living animals and humans, but methods to measure rates of oxygen consumption in vitro and in vivo are more limited. The literature was lacking of a systematic comparison between techniques able to measure oxygen consumption in vitro. For that reason, one of the thesis objectives was to compare the sensitivity of the methods for determining oxygen consumption (see chapter 3.I). Most of the in vivo methods available are not applicable in tumors (see chapter 1.IV.2). Consequently, we intended to develop new methods to measure the oxygen consumption of tumor cells non invasively (see chapter 3. II). Arsenic trioxide (As2O3) has been demonstrated as potent antitumor agent against acute promyelocytic leukemia (APL) and more recently solid tumors, and could inhibit mitochondrial respiration function. We therefore made the hypothesis that As2O3 could be an important modulator of tumor oxygenation by affecting the oxygen consumption of tumor cells. The several effects of As2O3 are described in the introduction and its effects on oxygen consumption will be part of our research in the last chapter.
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Diepart, C. (2010). Focus on tumor oxygen consumption : development of methods to measure oxygen consumption and evaluation of innovative co-treatment for radiotherapy. https://hdl.handle.net/2078.5/130976