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It is well established that tumours are not a collection of relatively homogeneous cancer cells, but act as organs with a complexity that might even exceed that of healthy tissues. Therefore to understand the biology of a tumour both the different individual cell types within a tumour as well as its microenvironment need to be studied. Hypoxia is a common characteristic of solid tumours, which has been associated with poor prognosis. Detection of hypoxia, preferably in a non-invasive manner, could predict treatment outcome and serve as a tool to support treatment decisions.
Within this seminar, I will focus on our experience on monitoring hypoxia using HX4 PET imaging and describe our preclinical and clinical results. While the prognostic significance of tumoural hypoxia on outcome has been established more than two decades ago only recently compounds are being tested in clinical trials that enabling monitoring and selective elimination of hypoxic tumours cells. The compelling evidence for hypoxia in tumour tissue and its therapeutic importance makes hypoxia a high priority target for cancer therapy. Bioreductive prodrugs selectively activated under hypoxia and drugs that inhibit molecular targets in hypoxic cells are currently extensively investigated. During the seminar our experience with several hypoxia-activated prodrugs as monotherapy or in combination with radiotherapy will be discussed. These compounds can be either activated by the hypoxic tumour cell itself or by clostridium bacteria (CDEPT) which do preferentially sporulate within these areas.
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