Drug That Crosses Blood-Brain Barrier Reduces Formation of Brain Metastases in Mice

Sep 29, 2009

(PhysOrg.com) -- 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 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 . 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 of human breast cancer. Human breast cells were cultured in the laboratory and were injected into mice with compromised immune systems. The 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 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 ccr.cancer.gov/staff/staff.asp?profileid=5851

Provided by National Institutes of Health

Explore further: Cancer survivors who smoke perceive less risk from tobacco

Related Stories

Drug combination shrinks breast cancer metastases in brain

Dec 16, 2007

A combination of a "targeted" therapy and chemotherapy shrank metastatic brain tumors by at least 50 percent in one-fifth of patients with aggressive HER2-positive breast cancer, according to data presented by Dana-Farber ...

Two microRNAs promote spread of tumor cells

Jan 28, 2008

The more scientists learn about microRNAs – short strands of RNA that can interfere with normal gene activity – the more obvious it becomes how closely they are associated with cancer. In a new study, scientists at The ...

Recommended for you

Spicy treatment the answer to aggressive cancer?

7 hours ago

It has been treasured by food lovers for thousands of years for its rich golden colour, peppery flavour and mustardy aroma…and now turmeric may also have a role in fighting cancer.

Cancer survivors who smoke perceive less risk from tobacco

Jul 02, 2015

Cancer survivors who smoke report fewer negative opinions about smoking, have more barriers to quitting, and are around other smokers more often than survivors who had quit before or after their diagnosis, according to a ...

Melanoma mutation rewires cell metabolism

Jul 02, 2015

A mutation found in most melanomas rewires cancer cells' metabolism, making them dependent on a ketogenesis enzyme, researchers at Winship Cancer Institute of Emory University have discovered.

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Sep 29, 2009
Whoopee! Artimisinin can do this and kill cancer cells without radiation.
Too late by 10 years.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.