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From: NIH news releases and news items [mailto:[log in to unmask]] On
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Sent: Tuesday, September 29, 2009 13:38
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Subject: DRUG THAT CROSSES BLOOD-BRAIN BARRIER REDUCES FORMATION OF BRAIN
METASTASES IN MICE
U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Cancer Institute (NCI) <http://www.nci.nih.gov/>
Embargoed for Release: Tuesday, September 29, 2009, 1 p.m. EDT
CONTACT: NCI Office of Media Relations, 301-496-6641, <e-mail:
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DRUG THAT CROSSES BLOOD-BRAIN BARRIER REDUCES FORMATION OF BRAIN METASTASES
IN MICE
The drug vorinostat is able to cross the blood-brain barrier and reduce the
development of large metastatic tumors in mice brains by 62 percent when
compared to mice that did not receive the drug, according to a new study.
In humans, the drug has been approved by the U.S. Food and Drug
Administration for the treatment of a cancer called cutaneous T-cell
lymphoma but can be used experimentally to study its effectiveness against
other cancers. This research, by investigators at the National Cancer
Institute (NCI), part of the National Institutes of Health, and their
collaborators, appears online Sept. 29, 2009, in Clinical Cancer Research.
For people, while various therapies are improving the survival of breast
cancer patients, the incidence of breast cancer spreading to the brain is
increasing. Brain metastases of breast cancer have proven to be largely
untreatable because the blood-brain barrier, which arises from the
specialized structure of blood capillaries in the brain, severely limits
drug access and many drugs are actively transported out of brain at this
barrier. Consequently, the one-year survival estimate for breast cancer
patients after a diagnosis of brain metastasis is only about 20 percent.
Vorinostat has been found to slow the growth of primary tumors of several
different types of cancer in mice. Previous studies have suggested that the
drug can be taken up by the brain, although little was known about its
effects on metastatic tumors. Therefore, to study the effect of vorinostat
on the formation of brain metastases, scientists used a mouse model of human
breast cancer. Human breast cells were cultured in the laboratory and were
injected into mice with compromised immune systems. The breast cancer
cells then migrated to the brain, forming metastases.
"Drugs that can cross the blood-brain barrier and reduce the size and
incidence of metastatic tumors are urgently needed," said Patricia S. Steeg,
Ph.D., study author, Center for Cancer Research, NCI. The researchers found
that vorinostat was absorbed readily into normal mouse brains, and
accumulation of the drug was up to three-fold higher in some metastases
treated with this drug when compared to surrounding brain tissue.
Vorinostat also reduced the development of tiny tumors (micrometastases) in
mice by 28 percent when compared with mice that did not receive this
therapy.
The ability of vorinostat to reduce metastatic lesions in the brain was
linked to a novel double-barreled mechanism -- the drug can cause breaks in
both strands of a DNA helix and can also lower the activity of a DNA repair
gene called Rad52. The researchers hypothesize that the inability of the
cancer cells to repair DNA damage would then slow the rate of tumor cell
metastasis.
In June of this year, several researchers affiliated with this study
published a paper in Molecular Cancer Therapeutics showing that vorinostat
could enhance the effect of radiation therapy in mice with brain cancer
metastasis. Mice that received implants of human breast tumors in their
brains lived the longest after treatment with both vorinostat and radiation,
demonstrating that the drug enhances the sensitivity of cancer cells to
radiation therapy. "Taken together with our current finding, researchers
have now established a preclinical basis for testing this drug in clinical
trials in humans," said Steeg.
For more information on Dr. Steeg's research, please go to
<http://ccr.cancer.gov/staff/staff.asp?profileid=5851>
NCI leads the National Cancer Program and the NIH effort to dramatically
reduce the burden of cancer and improve the lives of cancer patients and
their families, through research into prevention and cancer biology, the
development of new interventions, and the training and mentoring of new
researchers. For more information about cancer, please visit the NCI Web
site at <http://www.cancer.gov> or call NCI's Cancer Information Service at
1-800-4-CANCER (1-800-422-6237).
The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the U.S.
Department of Health and Human Services. It is the primary federal agency
for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its programs,
visit <www.nih.gov>.
---------------------------------
REFERENCE: Palmieri D, Lockman PR, et al. Vorinostat Inhibits Brain
Metastatic Colonization in a Model of Triple-Negative Breast Cancer and
Induces DNA Double-Strand Breaks. Clin Cancer Res. Sept. 29, 2009. Vol.15,
No. 19.
##
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<http://www.nih.gov/news/health/sep2009/nci-29.htm>.
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