Page 49 - 2014 Printable Abstract Book
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compression that can compact tumor vessels that may already have varying degrees of permeability to
the larger molecules. While many studies are able to establish that significant amounts of
nanotherapeutics are able to accumulate selectively in tumor tissue, many are unable to evaluate the
impact of the drugs on all of their target cells, including those tumor cells located far from vessels in
chronically hypoxic regions.
(S803) Tumor Oxygenation: Stem Cells and Metastasis. Dietmar Siemann, University of Florida,
Gainesville, FL
Ninety percent of all cancer deaths are due to metastases. Diseases such as prostate cancer are
highly curable if treated when localized but the prognosis worsens drastically if spread of tumor cells to
secondary sites occurs. Therapeutic strategies that interfere with the metastatic process are clearly
needed to improve patient survival. Hypoxia in primary tumors is a key factor associated with increased
metastases. In addition to the microenvironment, deregulated activation of the oncogenic pathways is
widely recognized to be significantly involved in tumor cell dissemination and poor prognosis. The
successful growth of a metastasis requires a cell with the capacity to initiate a tumor at a distant site. Only
a small subset of cells comprising solid tumors is capable of initiating and maintaining tumor growth.
These stem-like tumor initiating cells (TIC) are believed to be critically involved in treatment failures. This
presentation will discuss the impact of oxygen deficiencies on the maintenance of stem-like characteristics
of TIC, the potential interplay between genomic markers and hypoxia, and the effect of hypoxia on
signaling pathway critical to the metastatic process. It further will explore how the interference with
signaling molecules may have significant therapeutic potential in the development of novel therapeutic
intervention approaches for the treatment of cancer metastasis.
(S804) Targeting Tumor Hypoxia: Current Status and Future Prospects. Michael R. Horsman,
Dept. Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
It is now well established that regions of low oxygenation (hypoxia) are a characteristic feature of
solid tumors. The presence of such hypoxia is known to be a major factor influencing cellular radiation
resistance as well as playing a significant role in malignant progression. As a result numerous attempts
have been made, both pre-clinically and clinically, to try and overcome hypoxia. The most widely
investigated method in this context is radiosensitization of hypoxic cells with electron-affinic sensitizing
drugs or hyperthermia. Another approach often used to reduce hypoxia involves increasing oxygen
availability by having patients breathe high oxygen content gas, introducing perfluorochemicals into the
vascular system to increase the oxygen carrying capacity of the blood, modifying oxygen transport or
delivery by using agents that affect hemoglobin, using drugs that increase tumor perfusion, or a more
recent approach of decreasing the oxygen consumption of the “non-hypoxic” cell population thereby
increasing the oxygen diffusion distance. Hypoxic cells can also be preferentially destroyed by using either
bioreductive drugs which are active under reduced oxygen consumption, or again using hyperthermia.
More recent studies suggest that hypoxia may be overcome using various vascular targeting agents, which
can either inhibit angiogenesis, the process by which tumors form their own vascular supply, or by
destroying the already established tumor vasculature. Finally, one could simply target hypoxia by
modifying the radiation treatment. This could be achieved by increasing the radiation dose either to the
47 | P a g e
the larger molecules. While many studies are able to establish that significant amounts of
nanotherapeutics are able to accumulate selectively in tumor tissue, many are unable to evaluate the
impact of the drugs on all of their target cells, including those tumor cells located far from vessels in
chronically hypoxic regions.
(S803) Tumor Oxygenation: Stem Cells and Metastasis. Dietmar Siemann, University of Florida,
Gainesville, FL
Ninety percent of all cancer deaths are due to metastases. Diseases such as prostate cancer are
highly curable if treated when localized but the prognosis worsens drastically if spread of tumor cells to
secondary sites occurs. Therapeutic strategies that interfere with the metastatic process are clearly
needed to improve patient survival. Hypoxia in primary tumors is a key factor associated with increased
metastases. In addition to the microenvironment, deregulated activation of the oncogenic pathways is
widely recognized to be significantly involved in tumor cell dissemination and poor prognosis. The
successful growth of a metastasis requires a cell with the capacity to initiate a tumor at a distant site. Only
a small subset of cells comprising solid tumors is capable of initiating and maintaining tumor growth.
These stem-like tumor initiating cells (TIC) are believed to be critically involved in treatment failures. This
presentation will discuss the impact of oxygen deficiencies on the maintenance of stem-like characteristics
of TIC, the potential interplay between genomic markers and hypoxia, and the effect of hypoxia on
signaling pathway critical to the metastatic process. It further will explore how the interference with
signaling molecules may have significant therapeutic potential in the development of novel therapeutic
intervention approaches for the treatment of cancer metastasis.
(S804) Targeting Tumor Hypoxia: Current Status and Future Prospects. Michael R. Horsman,
Dept. Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
It is now well established that regions of low oxygenation (hypoxia) are a characteristic feature of
solid tumors. The presence of such hypoxia is known to be a major factor influencing cellular radiation
resistance as well as playing a significant role in malignant progression. As a result numerous attempts
have been made, both pre-clinically and clinically, to try and overcome hypoxia. The most widely
investigated method in this context is radiosensitization of hypoxic cells with electron-affinic sensitizing
drugs or hyperthermia. Another approach often used to reduce hypoxia involves increasing oxygen
availability by having patients breathe high oxygen content gas, introducing perfluorochemicals into the
vascular system to increase the oxygen carrying capacity of the blood, modifying oxygen transport or
delivery by using agents that affect hemoglobin, using drugs that increase tumor perfusion, or a more
recent approach of decreasing the oxygen consumption of the “non-hypoxic” cell population thereby
increasing the oxygen diffusion distance. Hypoxic cells can also be preferentially destroyed by using either
bioreductive drugs which are active under reduced oxygen consumption, or again using hyperthermia.
More recent studies suggest that hypoxia may be overcome using various vascular targeting agents, which
can either inhibit angiogenesis, the process by which tumors form their own vascular supply, or by
destroying the already established tumor vasculature. Finally, one could simply target hypoxia by
modifying the radiation treatment. This could be achieved by increasing the radiation dose either to the
47 | P a g e
