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Clinical Research Priority Program

When Oxygen Levels are Low

Low levels of oxygen can lead to aggressive tumor growth. Researchers on the Tumor Oxygenation Clinical Research Priority Program (CCRP) are pursuing various promising methodological, clinical, and preclinical approaches in an effort to find out why this is so.
Marita Fuchs

Oxygen is essential to life, and we can survive only a few minutes without it. The gas is transported from the lungs to every cell in the body, where it plays a vital role in the supply of energy. Physicians call an undersupply of oxygen to the tissues hypoxia. Hypoxia often also occurs with tumors because of the uncontrolled growth and chaotic structure of the blood vessels.

“As studies show, when oxygen levels are low tumors get more aggressive, and tumor cells are more likely to move via the blood and lymphatic vessels to other organs, where metastases can form,” explains Martin Wolf, Director of the Tumor Oxygenation Clinical Research Priority Program and Professor of Biomedical Optics at UZH.

Oxygen an important biomarker

Hypoxia occurs in somewhat more than half of all solid tumors. This isn’t good news for the patients affected, because tumors with hypoxia respond less well to radio- or chemotherapy than tumor cells saturated with oxygen. In two studies, survival rates for patients with hypoxic tumors were two to three times lower after five years.

So oxygenation is an important indicator of how a cancer is progressing. “Unfortunately hospitals haven’t been measuring this biomarker on a routine basis so far,” says Wolf. The 27 researchers on the Clinical Research Priority Program want to change this. The nine groups under the CCRP are working on methodological, preclinical, and clinical studies on the influence of oxygen on cancer. To delimit the scope of their studies they’re initially focusing on the role of oxygen in head and neck cancers.

The search for non-invasive methods

The aim of the clinical research group is to develop non-invasive methods such as imaging to identify poorly oxygenated regions of the tumor. “Every tumor is different, so each tumor patient has to be examined on an individual basis,” explains Wolf. The main challenge from a scientific point of view is to identify the areas where oxygen is low.

The researchers are able to use positron emission tomography (PET) to visualize oxygenation and circulation in the cells, using contrast agents to mark hypoxic regions. They’re also experimenting with new magnetic resonance imaging (MRI) methods. In this case they “feed” the cells with carbon dioxide to dilate the vessels and observe how tumors respond. By means of this maneuver they hope to gain insights into the oxygen content of the tumor.

Wolf and his team are also working on another spectroscopic imaging method, using near-infrared light to image blood volume and levels of tissue oxygenation. The near-infrared light is shone through the tissue, enabling the different layers to be analyzed. “Patients really appreciate near-infrared spectroscopy because the process is non-invasive and painless, and near-infrared light in the intensities used is harmless,” explains Wolf. The downside of this method, however, is that infrared light only penetrates a few centimeters into the skin, meaning there are tumors it still can’t image. Here too the researchers want to develop new approaches.

Selectively destroying hypoxic regions of the tumor

An important goal of the clinical research priority program is to improve the chances of cure for patients with hypoxic tumors. Researchers in the CCRP’s preclinical group are working to gain a better understanding of exactly how hypoxia negatively affects tumors, to see what kinds of new treatment approaches this could produce, and to find out the influence of different factors on the process.

More efficient treatment

The CCRP’s clinical group has a different goal. Here the researchers are trying to find how diagnosis could be improved by using biomarkers from blood and saliva samples alongside imaging methods. They’re testing new therapies fine-tuned to tumor hypoxia. “Hypoxic tumors are probably going to require more radical surgery – in other words, surgery involving the removal of more tissue and, depending on the circumstances, a greater loss of function.” The research group is also testing a new drug. In a randomized study, patients with hypoxic tissue are given an agent that responds to and is activated by hypoxic regions of the tissue. This allows hypoxic parts of the tumor to be selectively destroyed.

In radiotherapy it’s possible these days to make the dose very localized. This can be exploited, for example, to deliver a particularly high dose of radiation to hypoxic regions. Wolf is confident: “We have great hopes that the progress made by the CCRP will enable patients with hypoxic tumors to be treated more effectively in the future, with survival rates improving as a result.”

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