Tuesday, August 21, 2007

The Stem Cell Thing

One of the best parts of my job is that not only do I have the pleasure of taking care of children and young adults with sarcomas, but I also run a laboratory where we conduct research that we all hope will eventually lead to new treatments for my patients. I am going to talk a little about my laboratory research today.

One of the hottest new ideas in the world of cancer research is the concept of the “cancer stem cell.” As many of you who have been involved with Ewing’s sarcoma patients know, the correlation between response to therapy and cure is not very strong. In other words, although patients with widely metastatic disease can respond well to chemotherapy and to radiation therapy, relapse is frequent and cure rates remain less than 25%.

Why is this?

One possible explanation is the existence of a cancer stem cell. Cancer researchers used to believe that all cells within a tumor were the same, and that any one of them is capable of unlimited growth and of spreading to distant sites. We now know that this is not the case. Only a small fraction of the cells in a tumor are capable of unlimited growth. The rest will only divide a few times before dying. This recognition led to the development of the Cancer Stem Cell Model.

The Cancer Stem Cell Model predicts that the small number of cells capable of unlimited self-renewal would have properties similar to other stem cells, such as bone marrow stem cells and the embryonic stem cells that we read about in the papers all the time. These cells would be responsible for maintaining the primary tumor population and should be relatively resistant to chemotherapy. This would make them the primary cells causing relapse because of their ability to survive the treatments that kill the majority of the other cancer cells. Cancer stem cells have been identified in several types of cancer, including leukemia, breast cancer, brain tumors, and others.

So…. Are there sarcoma stem cells? That remains an open question, but one that we are in the process of studying in my lab.

We have some very exciting preliminary data that makes me think that we may have identified Ewing’s sarcoma stem cells. This, of course, is just the first step. After we are able to prove that these cells exist, the real fun will begin! We have a plan in place to learn as much as we can as quickly as we can about the basic biology of these cells.

Hopefully our research will have a big impact on many aspects of the care of sarcoma patients:

1. We can isolate sarcoma stem cells and try to find drugs that can kill them.

2. We can devise a rapid test for sarcoma stem cells that might allow us to better predict who will relapse and who will not.

3. We can devise strategies to identify these cells in biopsy specimens to be able to determine if treatments have killed stem cells in the patient.

4. We can devise new treatment strategies specifically targeting stem cells that hopefully will result in higher cure rates than currently used chemotherapy with fewer side effects.

It is an exciting time in cancer research…. This new theory goes a long way toward explaining why chemotherapy can make a tumor go away but might not cure the patient. Identifying the cells responsible for relapse will allow us to make big strides in treatment and hopefully dramatically improve our treatments.

I’m lucky to be able to work in both worlds (the lab and the hospital) and be in a position to guide research findings from the laboratory into the hospital and witness first hand this revolution in cancer treatment – away from toxic chemotherapy and toward targeted therapy* more precisely aimed at the cancer.

*An article I wrote for ESUN, the newsletter for the Liddy Shriver Sarcoma Initiative, on targeted therapies for sarcomas

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