Good Medicine Gets Better
A New Chemotherapy Drug Emerges From The Study of Kaposi's Sarcoma, a Once-Common Cancer in Those Infected With HIV.
Researchers have netted a potential cancer-fighting drug out of the bitter
lessons learned from HIV/AIDS—and are now testing the chemotherapy in
patients with a variety of cancers.
Called Veglin, the new drug grew from USC/Norris Comprehensive Cancer Center
physicians’ mounting knowledge of how Kaposi’s sarcoma tumors develop.
Though Kaposi’s sarcoma is in decline due to new anti-HIV therapies,
it has long been a common cancer in those infected with HIV.
“This is a drug that was developed in our labs, and it’s going right
to the clinic,” says Alexandra Levine, M.D., Distinguished Professor
of Medicine and chief of hematology at the Keck School of Medicine of USC.
“And it began with the AIDS epidemic.”
A phase I clinical trial of Veglin is now underway at USC/Norris, with Levine
as principal investigator. The trial is open to those with solid tumors, such
as breast or colon cancer, or hematological cancers, such as leukemia or lymphoma,
who have failed prior therapy. The study will evaluate the safety of the drug
at increasing doses.
Veglin was developed from the work of hematologic oncologist Parkash Gill,
M.D., professor of medicine and pathology at the Keck School, who began studying
how Kaposi’s sarcoma tumors develop and grow. Kaposi’s sarcoma is
a cancer of the cells that usually form blood vessels, so to understand the
cancer, Gill and researchers had to understand how blood vessels develop—both
in healthy people and in those with cancer.
Cancer cells develop and grow rapidly and need an ever-growing blood supply
to stay alive and continue expanding. As a result, cancerous tumors must encourage
new vessels to develop around them—a process called angiogenesis.
“It makes sense, then, that cancer cells would release chemicals to force
the development of new blood vessels,” Levine says. A family of chemicals
called vascular endothelial growth factors, or VEGF, induces these new blood
and lymph vessels.
Tumor cells produce VEGF to encourage vessels to grow. But many tumor cells
also carry a receptor for a type of VEGF on their own surface. In these cases,
the VEGF not only encourages new blood and lymph vessels to grow, but also
acts as a growth factor for the cancer cells. That means the tumors are fueled
by the very chemicals they make.
“If they were cars, these tumors would be making their own gasoline,”
Levine explains.
Using Kaposi’s sarcoma, Gill and his colleagues were the first to show
that VEGF could stimulate tumors to grow, acting as an autocrine—or self-stimulating—growth
factor.
To combat VEGF, Gill developed Veglin, a type of drug called an antisense
oligonucleotide that strikes at VEGF’s genetic assembly line. One particular
short sequence of DNA contains the genes that code for three types of VEGF.
Veglin, however, thrusts a stopper over that sequence. By plugging up these
genes, the drug hides the genetic recipe for the three types of VEGF—and
effectively keeps VEGF from being produced.
The drug has been tested in cells in the lab and in animal models, and results
were encouraging, Levine says.
Patients in the phase I study at USC/Norris will receive the drug through
a two-hour intravenous infusion five days in a row. Researchers will look
at the resulting levels of VEGF in the blood and gather information on which
types of tumors respond to the drug.
Keck School co-investigators in the study include hematologic oncologists
Anil Tulpule, M.D., Ann Mohrbacher, M.D., and Aziz Khan, and medical oncologists
Heinz-Josef Lenz, M.D., David Quinn, M.D., Ph.D., and Jeffrey Weber, M.D.,
Ph.D.
For information about eligibility for clinical trials at USC/Norris, call
the Clinical Investigation Support Office at (323) 865-0451.
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