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Senior Citizen Health & Medicine
Researchers Stop Tumor Growth in Mice, Ready to Join
Others in
Clinical Trials
Compounds stopped growth by 80% and with
chemotherapy tumors vanished
July 5, 2006 Researchers are ready to move to
human clinical trials with novel anti-cancer drugs that inhibited solid
tumor growth in mice by up to 80 percent, and in combination with
chemotherapy the tumors essentially disappeared. If approved for trials
that will join about 20 angiogenesis inhibitors currently being tested
in human trials. (See National Cancer Institute update below news
story).
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Health & Medicine |
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Researchers at the University of Minnesota say
these "small molecules" belong to a class of pharmaceutical agents
called anti-angiogenics. The new compounds are a refined form of drugs
that effectively reduce blood flow to the tumor, thereby inhibiting
tumor growth. The results of the study appear in the July 5 issue of the
Journal of the National Cancer Institute.
"This is a novel class of drugs that increases the
potential for good, effective treatment for cancer patients with
tumors," said Kevin Mayo, Ph.D., principle investigator and professor of
biochemistry, molecular biology and biophysics at the University of
Minnesota Medical School.
There is currently a protein anti-angiogenic agent
approved by the FDA for clinical use.
These new tumor-targeting compounds were designed
to mimic the functional part of an anti-angiogenic protein. But, because
the compounds are not proteins themselves, they have the advantage of
possibly being taken in pill form and being less costly to produce.
In animal studies with mice, the compounds
inhibited tumor growth by up to 80 percent, and in combination with
chemotherapy tumors essentially disappeared. Although the compounds
proved effective against solid tumors, researchers believe they have
potential to treat liquid tumors as well, such as the type found in
leukemia and other blood cancers.
"Our next step is to treat people with the drug in
FDA-approved clinical trials," said Mayo.
More about study:
The research was done in collaboration with the University of Minnesota
Departments of Biochemistry, and Chemistry, and the University of
Minnesota Cancer Center. The research was funded by the National Cancer
Institute.
Angiogenesis Inhibitors in Cancer Research
By National Cancer Institute
One promising avenue of cancer research is the study of a group of
compounds called angiogenesis inhibitors. These are drugs that block the
development of new blood vessels, a process known as angiogenesis. Solid
tumors cannot grow beyond the size of a pinhead (1 to 2 cubic
millimeters) without inducing the formation of new blood vessels to
supply the nutritional and other needs of the tumor.
By blocking the
development of new blood vessels, researchers are hoping to cut off the
tumor's supply of oxygen and nutrients, and therefore its continued
growth and spread to other parts of the body.
About 20 angiogenesis inhibitors are currently being tested in human
trials. Most are in early phase I or II clinical (human) studies. Some
are in or entering phase III testing. In Phase I/II trials, a limited
number of people are given the drug to determine its safety, dosage,
side effects, and preliminary activity.
In phase III trials, hundreds of
people around the country are involved in studies to determine how
effective the drug is. Although the design of phase III studies may
vary, in general all patients receive standard therapy: half of all
patients receive standard therapy plus the new drug and the other half
receive standard therapy and a placebo.
Bevacizumab (Avastin) for
Treatment of Solid Tumors
Bevacizumab (Avastin) was the first U.S. Food and
Drug Administration (FDA)-approved biological therapy designed to
inhibit the formation of new blood vessels to tumors. It is manufactured
by Genentech, South San Francisco, Calif. The National Cancer Institute
(NCI), part of the National Institutes of Health, has been involved in
the clinical development of bevacizumab in several tumor types under a
cooperative research and development agreement (CRADA) with Genentech.
Tumor cells require a constant supply of blood to
receive the oxygen and nutrients they need to survive. As a tumor grows,
it signals the need for more blood by secreting growth factors that
trigger the formation of new blood vessels, a process called
angiogenesis. Of the many growth factors implicated in the formation of
new blood vessels, vascular endothelial growth factor (VEGF) has been
identified as one of the most potent protein supporting tumor growth. In
addition to affecting tumor growth, VEGF promotes formation of new
capillaries surrounding the tumor, providing increased nutrients for
growth and a convenient route for tumor cells to spread throughout the
body.
Bevacizumab was developed to inhibit VEGF. It was
designed to cause the destruction of the blood vessel networks that feed
cancer cells as the lack of a constant source of blood may slow tumor
growth. Bevacizumab is an antibody -- a type of targeting device
produced by the immune system that can locate and bind to a specific
protein. In the case of bevacizumab, it is a monoclonal (cells derived
from a single common ancestor) antibody that binds to and inhibits VEGF.
Bevacizumab is one of many angiogenesis inhibitors
that have been developed based on a hypothesis of angiogenesis action
published in 1971 by Judah Folkman, M.D., Harvard Medical School,
Boston, Mass.
Bevacizumab has been investigated for efficacy in
treatment in a number of cancers. The NCI, in collaboration with a
network of investigators led by the Eastern Cooperative Oncology Group,
recently sponsored three key randomized clinical trials of bevacizumab,
the first of which was for metastatic colorectal cancer.
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