Targeted Treatment for Hypoxic Conditions

Forging new paths in pursuit of more targeted cancer treatments

The METOXIA project is focused on cell hypoxia. It is a European Collaborative Project within Health Research, funded with the support of the Seventh Framework Programme (FP7) and coordinated by the Department of Physics, University of Oslo, Norway. The EU-funded researchers have developed an innovative new cancer treatment. Interest from the pharmaceutical industry has been so great that the research team has set up a company dedicated to bringing their innovations to market.

Solid cancers are generally found in areas with lower levels of oxygen in comparison to normal tissues, meaning that some cancer cells adapt to such hypoxic conditions. Targeted cancer therapy could be achieved by developing targeting molecules that are specific to regulatory mechanisms activated by tumour hypoxia.

“During early drug development, we found that hypoxia was a key complicating factor in cancer treatment,” says project coordinator Erik O. Pettersen from the University of Oslo, Norway. “Hypoxia in cells causes cancer to become not only resistant to radiation but also to drug treatment, because medicine simply cannot reach hypoxic areas from the blood stream.” 

Recent research has shown that hypoxia in tumours is one of the major drivers of metastatic spread of cancer, the major cause of death by the disease. Thus, hypoxia is responsible for a double effect of reducing the potential of a successful treatment of the cancer patient, resistance to treatment and ability to spread. This is dangerous for cancer patients as it can mean that their bodies no longer respond to treatment. In addition, patients with hypoxic cancerous areas have been shown to be more resistant to chemotherapy, which means that the hypoxic micro-environment of tumours increases the chances of cancer metastasising and spreading.

Therefore, if one could develop methods that specifically located and inactivated cells in hypoxic areas one might obtain a cancer-specific effect, selective for the most harmful of the cancer cells. This development is the core task of the METOXIA project.

The long road from concept to market

The project team – involving experts from clinical and experimental medicine, molecular biology, synthetic chemistry, biophysics and electronics – therefore focused its efforts on finding weaknesses in hypoxic cells. The aim was to enable medical professionals to more effectively target them.

Pettersen and his team made the breakthrough discovery that if a receptor situated on the cell membrane protecting hypoxic cells could be neutralised, then the hypoxic cell could be killed off.

The team then faced another challenge. While the ability to kill off cancerous hypoxic cells represented a clear scientific breakthrough, this did not affect the aerobic cells responsible for tumour growth (hypoxic cells do not divide like ‘ordinary’ aerobic cells with access to oxygen). “When we took our findings to pharmaceutical firms, they were reluctant to invest because of this,” explains Pettersen. “We therefore needed to combine this discovery with another treatment to kill aerobic cells.”

What the team came up with was a drug with a dual component: at one end an inhibitor that kills hypoxic cells (with no effect on normal cells) and at the other end, a drug to increase cell radio-sensitivity. Combined with radiotherapy, the METOXIA team is confident that the treatment has promise. A new method for detecting and visualising hypoxia in patient tumours was also developed under the auspices of the project. 

“Following this, we set up the new SME DualTPharma in 2013 – the baby of METOXIA if you like – in order to focus on combatting cancer through the use of smart drugs,” says Pettersen. “We have applied for new EU financing, and hope to run trials at major clinical facilities all over Europe. We are really proud that we have reached this far, but the greatest potential reward would be the introduction of a new drug for effective cancer therapy.”