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Druker and Other Leukemia Pill Creators Honored by Harvard Medical School Faculty

   BOSTON, Mass.

Five scientists, including Oregon Health Sciences University oncologist Brian Druker, M.D., whose research ultimately led to the development of a groundbreaking pill used against chronic myelogenous leukemia (CML), will today be awarded the thirteenth annual Warren Alpert Foundation Scientific Prize at a ceremony in Boston.

The pill, STI571, was created by understanding the fundamental mechanisms that trigger CML, and was cited by Francis Collins, M.D., Ph.D., director of the National Human Genome Research Institute, as an early example of the kind of rational drug design that will stem from human genome studies. The STI571 clinical trials demonstrated "pretty dramatic results and ones which we hope will be repeated in other disorders as we get this kind of molecular understanding of what's gone awry in disease," said Collins.

Clinical trails of STI571 have produced encouraging results for patients with CML, a form of cancer characterized by rising white blood cell counts. Currently approved treatments are difficult for patients to tolerate. With STI571, however, researchers report that more than 90 percent of patients have gone into remission with few and modest side effects.

The Alpert Foundation recognizes David Baltimore, Ph.D., president and professor of biology at the California Institute of Technology, and Owen N. Witte, M.D., formerly of the California Institute of Technology and now professor in developmental immunology at the University of California, Los Angeles, for the basic science investigations that characterized the genetic pathway to CML. For their preclinical work that led to the creation of STI571, the Alpert Foundation awards Alex Matter, M.D., head of oncology research, Novartis Pharma AG, and Nicholas B. Lydon, Ph.D., formerly of Novartis and now vice president for small molecule drug discovery at Amgen, Inc. Brian J. Druker, M.D., professor of medicine at OHSU, is recognized for both his preclinical work and clinical trial investigations. The Foundation will divide among the winners a $150,000 award.

CML is caused by a genetic anomaly triggered by the rearrangement of chromosomes nine and 22, forming what is called the Philadelphia chromosome. A molecular consequence of this anomalous chromosome is the Bcr-Abl gene, whose product is a member of the tyrosine kinase family of proteins, which play a central role in a variety of cellular processes. Bcr-Abl's cancer-causing properties were identified and characterized by Baltimore and Witte.

The presence of Bcr-Abl in 95 percent of CML patients made this molecule a particularly attractive target for design of a selective kinase inhibitor. Matter, an early champion of kinase inhibitor research at Novartis, recruited Lydon to take on the effort of identifying Bcr-Abl inhibitors. While working on this effort, Lydon began collaborating with Druker, whom he met in the 1980s when Druker was an oncology fellow studying kinases at Harvard Medical School's Dana Farber Cancer Institute. Together, Lydon and Druker identified STI571 as the premiere Bcr-Abl inhibitor, blocking Bcr-Abl's ability to transfer signals, or phosphate groups, to white blood cells. In 1998, Druker began clinical trials that have led to the drug being submitted for FDA approval (as Gleevec) this year as a treatment for chronic and acute-phase CML.

Recently, STI571 also has shown effectiveness against gastrointestinal stromal tumors (GIST), which occur in an estimated 5,000-10,000 Americans each year. These tumors originate in the stomach or small intestine in cells that form the organs' connective tissue. Patients with malignant GIST that cannot be removed by surgery generally die within a year or two of diagnosis. In 1993, Druker found that STI571 also blocked the tyrosine kinase KIT, which is the flawed protein present in GIST. Druker's colleague at OHSU, Charles Blanke, M.D., will present results from the first clinical trials of STI571 on GIST on May 13 in San Francisco.

Warren Alpert runs Warren Equities and its subsidiaries, which market petroleum and food products, and engage in transportation and real estate investments. Every year, the prestigious Warren Alpert Foundation Prize honors scientists and researchers who have made significant discoveries in the prevention, treatment or curing of disease. Prize recipients are selected by the foundation's Scientific Advisory Committee, comprising internationally renowned biomedical scientists from the Massachusetts Institute of Technology and Harvard Medical School, and chaired by the dean of Harvard Medical School.


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