As part of its commitment to education, in 2006 Memorial Sloan Kettering established an annual symposium designed to expose members of the public, especially high school students, to important new research that is contributing to the understanding and treatment of cancer.
Memorial Sloan Kettering’s fourth annual Major Trends in Modern Cancer Research drew an eager audience of approximately 300 students and their teachers from 15 high schools in the New York City area. They gathered in the Rockefeller Research Laboratories Auditorium on the evening of November 5 to hear Memorial Sloan Kettering experts talk about their individual areas of research and to put that research into a broader context.
“We believe what we do at Memorial Sloan Kettering to understand cancer and treat it more effectively involves work that is accessible to everyone,” observed Memorial Sloan Kettering President and symposium moderator Harold Varmus in his welcoming remarks. “I’m increasingly impressed with how middle school students, and even grade school students, can appreciate what we’re doing to understand the genetic basis of cancer and use new information about cancer to improve the way we treat it, classify it, and diagnose it.”
Memorial Sloan Kettering physician-scientist Ross L. Levine, a member of the Human Oncology and Pathogenesis Program (HOPP), talked about how modern genomic techniques are used to identify novel mutations in human cancers and how investigators go about developing molecularly targeted therapies.
“I began my training at the beginning of an exciting era during which many different investigators were starting to use genetic tools to understand a whole spectrum of diseases, including cancer,” said Dr. Levine, who studies and treats myeloproliferative diseases — blood disorders caused by an overproduction of blood cells in the bone marrow. “It became clear to me that I wanted to understand the blood diseases that I was seeing in the clinic by studying them in the laboratory, with the idea that we could ultimately bring what we learned to help treat patients.”
In his presentation, Dr. Levine discussed the development of the molecularly targeted drug imatinib (Gleevec®), which has transformed chronic myeloid leukemia (CML) from a fatal disease into one that is nearly always treatable. Imatinib blocks the activity of the BCR-ABL protein, a signaling molecule that promotes the continuous growth and proliferation of CML cells. The protein is encoded by a gene that results when pieces of two chromosomes break off and trade places. “It became clear to a number of investigators [including Charles L. Sawyers, now Chair of HOPP] that this gene might be a target — that you might be able to find a drug that could take this always-on gene and turn it off. That drug was Gleevec,” explained Dr. Levine. “The discovery encouraged a generation of us to think that if we could come up with targets in other cancers maybe we could also come up with therapies that might do the same for these targets.”
Dr. Levine concluded by talking about his contributions to the 2005 discovery that a single mutation in the JAK2 gene is responsible for a number of myeloproliferative disorders. JAK2 is an enzyme called a kinase, which acts as an on-off switch, triggering the production of blood cells. Using blood samples from patients with myeloproliferative disorders, Dr. Levine and his colleagues found that in two-thirds of these patients, their cancer cells had a single mutation in the JAK2 gene causing the switch to remain in the on position, thus precipitating the uncontrolled cell proliferation that characterizes myeloproliferative diseases. “There are now, at my last count, seven different drugs targeting this protein in the clinic,” Dr. Levine said. “It’s our expectation that within 12 to 18 months there will be an approved drug for these diseases, which proves that if you study patients and find targets, you can make new drugs.”
Lawrence H. Schwartz, formerly Vice Chair for Technology Development in Memorial Sloan Kettering’s Department of Radiology and Director of MRI, and now Chair of the Department of Radiology at Columbia University College of Physicians and Surgeons and radiologist-in-chief at NewYork-Presbyterian Hospital/Columbia University Medical Center, explained that “the role of imaging in oncology has changed tremendously — from the days of very basic x-rays to much more sophisticated techniques that today allow us to see structures as well as the function of individual tumors. We’re able to characterize tissue, identifying a lesion as either benign or malignant based upon the imaging. We can stage patients who have a diagnosis, defining the extent of the tumor to decide whether they may be better off having an operation or radiotherapy, or what medical therapy may be beneficial,” he said.
Dr. Schwartz went on to say that an important goal in modern imaging is to be able to know very early on in treatment whether a specific drug or therapy is working “so that we can intervene and give the patient a different drug if the therapy stops working. We want to be able to assess response to therapy so that we can make decisions together with oncologists soon after the start of therapy in a given patient, as well as use imaging in drug discovery, to identify successful new drugs.”