Researchers uncover Achilles' heel in aggressive breast tumors

October 12, 2010

In an unexpected twist, Fox Chase Cancer Center researchers find that the loss of a single protein, Nedd9, initially slows cancer formation but then makes the tumors that do arise more aggressive. The good news, though, is that the lack of Nedd9 also makes the aggressive tumors more sensitive to a class of drugs that are already used in the clinic.

"If a tumor is able to overcome the loss of this protein, this clearly makes it undergo complicated changes that ultimately select for a more aggressive tumor," says Erica A. Golemis, Ph.D., professor and co-leader of developmental therapeutics at Fox Chase, and senior author on the new study, published online October 12 in . "It is reminiscent of the situation you get when you treat cancer patients with a drug and get an initial response. However, eventually their tumor overrides the drug, and then you have a really tough tumor."

A number of studies have shown that increased Nedd9 expression is associated with metastasis in a variety of human cancers, including breast cancer. Last year, Golemis's group reported that deleting Nedd9 from a of breast cancer delayed , compared with control animals. Now, they report that the cells isolated from the Nedd9-deficient tumors more rapidly form new tumors in mice, and more readily give rise to lung metastases, in contrast to tumors with normal levels of Nedd9.

Because Nedd9 interacts directly with Src, a protein that has been a major drug development target, lead author on the study, Mahendra K. Singh, Ph.D., tested whether the Src inhibitor dasatinib, already approved for , would control the aggressive Nedd9-deficient tumors. He found that dasatinib rapidly killed the Nedd9-deficient , even at low doses.

Golemis, Singh, and colleagues now hope to partner with clinician colleagues in trials to compare action of the drug in patients whose tumors have low Nedd9 expression. "My hunch is that this is going to be very important for understanding how best to treat patients in the future," Singh said.

Explore further: Loss of cell's 'antenna' linked to cancer's development

Related Stories

Loss of cell's 'antenna' linked to cancer's development

June 28, 2007

Submarines have periscopes. Insects have antennae. And increasingly, biologists are finding that most normal vertebrate cells have cilia, small hair-like structures that protrude like antennae into the surrounding environment ...

Researchers find clue to stopping breast-cancer metastasis

November 17, 2008

If scientists knew exactly what a breast cancer cell needs to spread, then they could stop the most deadly part of the disease: metastasis. New research from the University of North Carolina at Chapel Hill School of Medicine ...

NEDD9 protein supports growth of aggressive breast cancer

October 2, 2009

Researchers at Fox Chase Cancer Center have demonstrated that a protein called NEDD9 may be required for some of the most aggressive forms of breast cancer to grow. Their findings, based on the study of a mouse model of breast ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


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.