Counteracting Hypoxia in Radio-Resistant Metastatic Lesions
The identification of hypoxia-regulated genes and proteins, has provided the basis for the generation of new hypoxia-targeted drugs, conceived to re-oxygenate hypoxic tumor areas. In patients with advanced metastasizing prostate cancer (PC), these kinds of drugs are expected to optimize the effect of radiotherapy, reducing also its side effects. Immunohistochemistry, DNA, proteomic and, tissue array profiling, are increasingly providing us with exciting data, that could lead to the formulation of pre-treatment multimarker tests able to identify the individualized tumor response profiles to radiotherapy, basing on the specific cancer tissue hypoxia pattern and degree (Bussink et al., Radiother Oncol 67:3–15, 2003).
As an example, the recent discovery of the role of microRNA in PC tumor genesis points towards (Kulshreshtha et al., Cell Cycle 6(12):1426–1431, 2007) the, Inactivation of miRs affected by hypoxia as a promising synergistic therapeutic strategy for the radiotherapy-refractory subset of metastatic PC (Kulshreshtha et al., Cell Death Differ 15:667–671, 2008).
This chapter aims to give an outlook of the main hot-topics concerning the new trends of hypoxia-targeted molecular therapies for advanced metastasizing prostate cancers.
KeywordsProstate Cancer Vascular Endothelial Growth Factor Androgen Receptor Radical Prostatectomy Vascular Endothelial Growth Factor Expression
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