Dr. James Fick, a neurosurgeon at the Medical College of Georgia, looks over a group of slides showing brain cancer.KATHY MOORE/STAFF

Researchers target cancer

New methods aim to remove malignant growths without destroying brain function

Web posted August 24, 1997

By Tom Corwin
Staff Writer

In the war against cancer, Dr. James Fick is hoping to introduce a new stealth weapon that could vanquish a stubborn foe which has repeatedly eluded doctors.

The weapons that cancer doctors train on offending tumors in the brain often take out innocent cells and tissues surrounding the tumor. With some tumors, such as the glioblastoma multiforme, such attacks are often futile, Dr. Fick said.

Click the image above for a full-sized version of the graphic "A New Cancer Thearaphy."By Rick McKee and Tom Corwin/Staff

``It's a rapidly growing, extensively infiltrating tumor that has defied modern science over the last three decades,'' said Dr. Fick, a neurosurgeon and researcher at Medical College of Georgia.

Brain tumors are often difficult to remove without destroying some brain function and may also be difficult to treat with chemotherapy. With glioblastoma, the average life expectancy is less than a year, and even when successfully removed a tumor often reappears close to the original spot, Dr. Fick said.

Cameron Andrews knows too well the ferocious speed and power of the tumors. His wife, Rebecca, was a vibrant and active director of emergency services at MCG in 1993 when her occasional headaches started to come more often. The pain finally drove her to her own emergency room, where the doctor suggested a CT scan.

Click the image above for a full-sized version of the graphic "How Glioblastoma Works."By Rick McKee and Tom Corwin/Staff

Inside her head was a tumor ``the size and shape of a pear,'' Mr. Andrews said. ``From a psychological standpoint, her life ended that day.''

Though surgery would remove most of the tumor and radiation could slow its growth, the couple was told

it was a matter of time, he said.

``She was diagnosed right before our daughter's 16th birthday, and that hurt her because of all the things she knew she was going to miss,'' Mr. Andrews said. She died six months later at age 42.

Three years later, Dr. Fick and 39 others around the world are trying a new strategy to take the battle to the tumor's level and fight it cell to cell. A tumor that begins in a brain cell spreads and forms its own structure, creating a group of cells that communicates and function separately from the surrounding cells.

Against them, Dr. Fick is employing one of the oldest military tricks - the Trojan horse. The idea is to use a retroviral vector, a virus that invades the cell and uses the cell's genetic material to reproduce itself.

Doctors take a virus and disable it so that it can invade the cell but cannot then reproduce itself and leave the cell, Dr. Fick said. And tagging along with the virus is a gene called thymidine kinase, taken from the herpes simplex virus. This strategy allows cancer doctors to take aim precisely at the tumor and not at the surrounding healthy cells, Dr. Fick said.

This slide shows brain cancer cells before treatment.Special

``Normal brain cells aren't replicating (or reproducing), but the tumor cells are,'' Dr. Fick said. ``Retroviral vectors can only transfer genes into replicating cells.''

With the tumor cells now housing the gene, the patient is given a powerful anti-retroviral drug called ganciclovir that is especially effective against the herpes virus. The drug converts the foreign gene into a toxin that then kills the host tumor cell.

Dr. Fick is also studying ways of making the tumor cells communicate better among themselves, which they do through gap junctions or ``portholes'' between the cell walls, so that the toxicity is passed more quickly and effectively within the tumor.

This slide shows brain cancer cells after treatment.Special

Earlier studies showed there was a ``bystander'' killing of tumor cells, where tumor cells that had not been invaded by the virus still died, and this effect eliminated tumor cells in nearly all the rats it was tested on.

The first phases of testing on humans showed that the gene transfer will work, Dr. Fick said. But MCG is still awaiting its first patient to see whether it can become an effective treatment, Dr. Fick said. Finding a patient can be difficult because the tumor is rare and strikes one in 100,000 people.

Of the $2.4 billion the National Cancer Institute spends on research, only about $36 million is going to gene therapy, said spokeswoman Caroline McNeil.

``A lot of gene therapy is still in the laboratory or in animals (tests),'' she said.

That will change once the first patient is treated and the tumor defeated, said Dr. Paul Dainer, director of MCG's Comprehensive Cancer Clinic.

Even as exciting as this type of gene therapy is to researchers, it is always done with the aim of improving the current options for cancer patients - surgery, radiation treatments and chemotherapy, Dr. Fick said.

``Maybe they could help shrink the tumor before surgery, making its removal easier,'' Dr. Fick said. ``These are legitimate goals for 1997.''

In this experiment, patients will still have the tumor removed surgically, and the gene therapy will be used to keep the tumor from reforming.

If it proves effective, the technique could move out of Dr. Fick's laboratory and into the Comprehensive Cancer Center a block away.

``Where we think we are unique (at MCG) is in the research going on in our laboratories that we hope will contribute to new and important gene therapy strategies for people in the future,'' Dr. Fick said.

He also is exploring the possibilities of using the same therapy for more common cancers such as metastatic breast cancer or prostate cancer ``because there is a huge need for people in these areas.''

The slides of dying cancer cells lighted up under the microscope may show the way for the future, perhaps one day allowing cancer doctors to beat the disease within the patient's cells, said Cheryl Wheeler, coordinator of the Harry W. Jernigan Jr. Cancer Center at University Hospital. That's her hope, even if it makes her center and all its equipment obsolete.

``I would not be unhappy if I was out of a job,'' she said.