VAI Cancer Research Shows Results

September 24, 2004
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GRAND RAPIDS — Three Van Andel Institute scientists briefed the public on their current cancer research activities at the VAI's recent State of the Institute presentation.

Cancer is the No. 2 killer of men and women in the United States, and this year the disease is expected to claim 600,000 lives in this country alone, said Nicholas Duesbery, Ph.D.

"This deadly disease can be beat," he told about 70 people gathered at the VAI for an update of the institute's progress.

"We believe a better understanding of the basic biology underlying cancer will lead to the development of new approaches for cancer treatment."

Duesbery has made some new discoveries about cancer and anthrax in his studies of the mechanisms that govern the development of frog eggs. The cells in embryos possess qualities and activities that are characteristic of cancer cells, he said. Cells in embryos and cancer divide very rapidly, move around and promote the formation of new blood vessels.

"The mechanisms that regulate those processes are virtually identical in all animals," he observed.

"So what we've learned about cell division, cell movement and the vascularization of one animal can tell us something about how the same processes are regulated in humans."

Several years ago, his lab discovered that anthrax lethal toxin is a potent inhibitor of frog egg development. The lab is using mice to grow human tumors, which are then treated with the toxin.

Lethal toxin stops activity of MEK proteins, which play an essential role in egg formation and a number of other vital cell functions, Duesbery explained. Lethal anthrax toxin also blocks tumors from recruiting new blood vessels.

"Since MEK plays such an important role in cancer, we believe lethal toxin can be developed into an effective cancer treatment. We have preliminary data that indicates that lethal toxin can be useful in the treatment of a variety of cancers, including leukemia, melanoma, lung cancer, colon cancer, kidney cancer, prostate and breast cancer."

The National Cancer Institute has awarded the Van Andel Research Institute a four-year, $1.3 million grant to pursue the anthrax study.

The laboratory of Rick Hay, M.D., Ph.D., has developed a new strategy for the diagnosis and therapy of aggressive cancers — those cancers most likely to spread from their point of origin to distant sites within the body.

Most suffering and deaths due to cancer are caused by the consequences of aggressive cancers, Hay noted, and all cancers have the potential to proliferate and travel.

"In the field there's a need for more reliable ways to identify aggressive cancers earlier to prevent their progression and to treat cancers that are already progressed," he stressed.

His lab is working on nuclear imaging and therapy of Met-expressing human tumors. Met is a molecule that facilitates aggressive behavior by cancers. Without Met, cells don't divide very rapidly and don't travel, Hay explained. His lab is using a new strategy called MetProbe for detecting and treating aggressive cancers.

MetProbe is a "home-grown VARI product" that gives scientists the ability to locate and map aggressive cancer cells, he said. He and fellow scientists at VARI are producing and evaluating monoclonal antibodies that recognize Met.

The team is "tagging" the antibodies with radioactive atoms so they can seek out cancers that have high levels of Met.

When the antibodies are injected into an animal or human or exposed to cancer cells, the radioactivity is then detectable with nuclear imaging equipment, he explained.

"Now that we have a way to detect that radioactivity and measure it, we can map where it is and see how much there is and identify where it has gone."

The hope is to develop Met-directed therapy, such as Met-blocking chemotherapy or biological agents that eliminate Met.

Next up is MetProbe safety tests. Hay expects the first human testing will be undertaken in 2007, and said VARI is looking for an industry partner to market MetProbe.

VARI received an $800,000 grant in June from the Technology Tri-Corridor to continue the study.

Hay said VARI is committed to meeting the National Cancer Institute's challenge to eliminate suffering and death due to cancer by the year 2015.

Eric Xu, Ph.D., explained that the molecular structure of protein and DNA is the physical basis of how every living cell functions. His laboratory is using x-ray crystallography to study the structure and functions of certain proteins that are related to human diseases, including cancer and diabetes.

Xu discussed the impact of x-ray crystallography on biological research and drug discovery and outlined the four steps involved in his lab's x-ray experiments.    

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