On Cancer: At Work: Pediatric Oncologist Scott Armstrong

Pictured: Scott Armstrong, Michael Kuehn, Haijhua Chu, Monica Cusan & Andrei Kritsov Pediatric oncologist Scott Armstrong with (from left) research fellow Michael Kuehn, Haihua Chu, and Monica Cusan, and instructor Andrei Kristsov, who are all members of his laboratory.

Scott Armstrong is a pediatric oncologist specializing in the treatment of children with leukemia. He is particularly interested in the development of new therapies that are more effective and less toxic. We talked to him about his work and his laboratory research, which has led to findings that point to potential new therapies for children and adults with the disease.

Many would argue that the next big development in cancer research will be in the field of epigenetics — the study of changes in gene expression that are controlled by factors other than changes in an individual’s DNA sequence. These proteins and mechanisms contribute to cancer development in ways that we didn’t really understand ten years ago.

For example, we have discovered that a mutation that affects cells’ epigenetic programs — in this case by changing the structure of chromosomes — occurs in a number of different types of leukemia. Changing that chromosomal structure causes a gene expression program to get turned on when it shouldn’t. And for these types of leukemia, we now know exactly what the protein is that allows that to happen. The protein is called a histone methyltransferase (HMT), and we’re working to develop small-molecule inhibitors of the protein that are now in clinical trials at Memorial Sloan Kettering Cancer Center in several adult leukemias. The research is particularly exciting because this is the first small-molecule inhibitor of an HMT to be evaluated in humans.

It’s becoming increasingly clear that many types of cancer have abnormalities in histone methyltransferases and that these abnormalities are likely part of the tumor development process in many cancers. So what we are learning with these new approaches in leukemia is likely to have a much broader impact as we understand more about how abnormalities in HMTs are working to drive cancer development.

The idea behind Memorial Sloan Kettering’s new Leukemia Center [of which Dr. Armstrong is director] is to continue to develop ways to connect what’s going on in the laboratory to what’s going on in the clinic. It will provide the infrastructure — the people, research, and technologies — to help move exciting new discoveries from the lab into clinical trials as quickly as possible. We will use next-generation genomic sequencing technology to characterize leukemia samples from patients in order to understand, in as much depth as possible, which mutations are present in leukemias and how they work together; develop mouse model systems of those leukemias; and then test newly developed therapies to support the rationale for ultimately doing clinical trials in patients.

Our goal is to streamline the process and encourage multiple Memorial Sloan Kettering labs to work together using a common approach. The synergy that will develop will make it easier for the institution to support these efforts and for pharmaceutical companies and others to work with us.

We’ve gotten to the point where basic research discoveries are making a difference for patients. One of the things that makes me most proud as a pediatric oncologist who specializes in treating children with leukemia is when I talk to the parents of a child who has leukemia and I’m able to tell them that we’re making discoveries that are likely to influence the course of the disease for the better. It’s incredibly motivating to think of the comfort it gives parents to know that there are people focused on studying leukemia as deeply and intensely as we are, and if our efforts don’t make a difference for their child, we expect they will for patients in the future.

I don’t know of a better goal than being able to look back in ten or 15 years and say that I had a tangible influence on the way that people are treated for cancer. That is definitely what drives me and the people I work with here.

This profile was featured in Memorial Sloan Kettering's 2012 Annual Report.


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