Human breast cancer cells (left) are treated with a trial dose of the leukemia drug dasatinib (center) and then with a 10-fold stronger dose. (Image courtesy of Seth Corey)

 

 

Northwestern.edu, August 30, 2010, by Jessica krinke  —  Researchers at Northwestern University are pioneering ways to shoot out the tires from breast cancer’s getaway car in a high-speed chase of drugs and carcinogenic criminals.

That’s because breast cancer itself doesn’t kill until it metastasizes, or travels, to other sensitive organs, invades and then grows. But a new clue to stopping this destructive spree surprisingly came from pediatric research.

Dr. Seth Corey is a pediatric oncologist at Children’s Memorial Hospital and professor of cellular and molecular biology at Northwestern University’s Feinberg School of Medicine. They’ve found that dasatinib, a drug already used to eliminate leukemia in the bone marrow, may also prevent mobility in breast cancer, keeping it from invading vital organs.

But even though dasatinib is FDA-approved for the treatment of leukemia, the likelihood of your doctor prescribing it for breast cancer just yet is slim. The Northwestern research team hopes that dasatinib’s clinical trials will help determine what kinds of breast cancer respond to it best. By mapping the biological signatures of varying cancer types this way, fingerprints of these malignant flight-risks to assist in diagnosis and further targeted treatment may not be far off.

Seth Corey (image courtesy of Jessica Krinke/MEDILL)Medill Reports asked Corey about his team’s research, and what the future may hold for dasatinib and breast cancer.

Q)        What is the basic aim of your research?
A)   My primary interest is in leukemia, which is a cancer of the bone marrow – the site of [all] blood cell production. Cancer cell behavior is this: they proliferate, they do not differentiate, and they do not die. But for solid tumors, which is everything but leukemia, the cancer cells also have additional characteristics that make them malignant, and that is the ability for them to invade local tissues, spread to different sites and to metastasize as in the liver, the bone, the brain. Those are the more common sites for breast cancer metastasis.

Q)   What makes breast cancer unique among cancers?
A)   I’m a pediatric oncologist, and even though death due to cancer remains the most common cause of non-accidental death in children and adolescents, it’s uncommon. Maybe about 12,000 cases of new pediatric cancer are diagnosed each year in the United States. The total for adult cancers is about 1.5 million people each year. 

Every cancer is different, and even within different [cancers] there are different types and different levels of aggressiveness. Breast cancer is a public health concern because around 180,000 women are diagnosed each year, so it’s one of the most common cancers to occur.

Q)   Is leukemia a very common cancer in children?
A)   Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer, although in adults it’s very rare. ALL occurs with about 3,500 cases per year, so it’s a little less than a third of all pediatric cancers.

ALL has been the focus in childhood cancer and, over the past 40 years or so, it has gone from a disease that was almost uniformly fatal to a disease that’s almost uniformly curable. We’ve gone from a roughly five-year survival rate in about 1960 or so of 8 percent to a five-year survival rate in 2010 of like 90-92 percent. It’s been an achievement of modern chemotherapy.

Q)   So how did leukemia in children lead you to study breast cancer?
A)   Christina Pichot gets a lot of the credit for helping to steer the lab and my thoughts in the direction of breast cancer. Chrissy was a graduate student then, she just got her PhD in March and she was interested in breast cancer. She began to look at Src kinase and how its levels and expression patterns correlated with different types of breast cancer. Src kinase is an enzyme, which is a protein that speeds up chemical reactions a million-fold. It remodels the cytoskeleton and the plasma membrane [of a cell].

[She] found that levels [of Src kinase] were highest in those breast cancer tissues that were the most aggressive and invasive. What she did was manipulate the expression of this protein by turning it off. And she found that cells didn’t invade as well, didn’t migrate as well and didn’t form finger-like projections, invadapodia, which help break down the barrier and facilitate the initial steps in cancer cell invasion. When cancer cells take up residence and continue to grow, forming metastasists, that’s what kills people.

Chrissy started to look at a drug, dasatinib, which is an FDA-approved drug for a form of leukemia called Chronic Myeloid Leukemia (CML). We found that [blocking] the Src kinases didn’t so much stop the cells from surviving, but it kind of got them to stop growing as quickly. But what it also did, and I think this is something that needs to be exploited, is that it did affect their ability to migrate, to invade and to form those finger-like projections of invadapodia.

Q)   How can readers imagine this for themselves?
A)   You can think of it like a car. A car needs to move and the way it moves is turning on the engine and running on the four tires. So the idea is to knock out all the tires so our cancer car won’t move. If you can shoot out the tires of the car with a drug like dasatinib, then you’re going to slow down the cancer cell and extend peoples’ lives.

Q)   Is dasatinib something someone who currently has breast cancer can ask her doctor about?
A)   One goal is to make the disease go away, but an alternative goal is to have stable disease in check. If you can’t cure somebody of a cancer, you can make it a chronic disease. I think most people could live with that. The question is how to incorporate dasatinib into a multi-drug regimen as a second-line or third-line therapy for women with refractory, or relapsed, breast cancer.

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