Janet Davison Rowley, MD, the Blum-Riese Distinguished Service Professor of Medicine, Molecular Genetics & Cell Biology and Human Genetics at the University of Chicago, will share the 2012 Japan Prize for Healthcare and Medical Technology with Brian J. Druker, MD, from the Oregon Health and Science University, and Nicholas B. Lydon, PhD, formerly with Novartis. They were chosen for their roles in the development of the first precisely targeted anti-cancer drug, called imatinib (Gleevec®).
The three recipients, according to the Japan Prize Foundation's announcement on Jan. 25, "have made significant contributions to society by achieving momentous scientific and technological breakthroughs in creating and promoting new technologies for medical diagnosis and treatment."
They each will receive a Certificate of Merit, a Japan Prize Medal and an equal share of 50 million Japanese yen (approximately $215,000 apiece).
Imatinib is a highly effective leukemia medication with few side effects. Most conventional treatments for cancer have been based on their ability to kill rapidly dividing cells. The challenge has been finding a treatment that doesn't harm healthy cells. A series of discoveries enabled the prize winners to develop a more focused medication, designed to interfere with the specific proteins that cause rapid multiplication of the cells that cause chronic myelogenous leukemia (CML), but without damaging healthy cells.
Rowley, Druker and Lydon were key players in a four-decade sequence of breakthroughs leading to the development of Gleevec. It began in the 1960s when two Philadelphia researchers -- Peter Nowell and David Hungerford -- found that patients with CML had an abnormally small chromosome 22 in their tumor cells, which was labeled the "Philadelphia" chromosome.
In 1973, using newly developed methods for visualizing segments of chromosomes, Rowley showed that chromosomes from CML cells did not lose genetic material, but rather they exchanged it, a phenomenon she has described in several types of leukemia.
The Philadelphia chromosome was the result of such a translocation. In patients with CML, a crucial segment of chromosome 22 broke off and moved to chromosome 9, where it did not belong. At the same time, a tiny piece of chromosome 9, which included an important cancer-causing gene, had moved to the breakpoint on chromosome 22. Because of this transfer from one chromosome to another, important genes that regulated cell growth and division were no longer located in their normal positions on the chromosome.
Other scientists used this discovery as a road map to narrow the search for specific genes that were disrupted by chromosome translocations. In 1993, Lydon -- a medicinal chemist at Ciba-Geigy, later purchased by Novartis -- began a collaboration with Druker, who had created cellular models of the genetic changes that drive CML. The two physicians developed the lead candidate drug from this program, then known as STI-571, and showed that Lydon's drug exerted powerful effects against Druker's CML cells.
In subsequent clinical trials, led by Druker, imatinib "shocked the world of clinical medicine," according to the Japan Prize Foundation. It demonstrated dramatic clinical effectiveness in reducing leukemia cells, achieving long-term remissions in more than 90 percent of patients with CML. It was approved by the Food and Drug Administration in 2001 and has proved effective against several other cancers caused by similar genetic mechanisms.
"Before the development of the molecularly targeted drug imatinib, CML was a fatal disorder where patients progressed to blastic crisis within a few years and died due to a treatment-refractory acute leukemia," notes the Foundation's Award Citation. The molecular-targeting approach used to develop Imatinib, has given "great hopes for the future of cancer drug development."
For this "extraordinary achievement, the development of a revolutionary therapy for cancers," the Foundation has deemed Rowley, Druker and Lydon "most eminently deserving of the 2012 Japan Prize given to honor contributions in the fields of Healthcare and Medical Technology."
The Japan Prize Presentation Ceremony will be held in April in the presence of Their Majesties, the Emperor and Empress of Japan, with leaders "from every field of endeavor" in attendance.
Rowley, 86, has received many honors, including the Lasker Award, the National Medal of Science and the Presidential Medal of Freedom, the nation's highest civilian honor. In December, the American Society of Hematology honored Rowley and Druker with its 2011 Ernest Beutler Lecture and Prize for their work on CML. Druker and Lydon received the Lasker Award in 2009.
"Janet is a pioneer in what is now called 'translational research,' the direct application of laboratory studies to understanding and treating human disease," said leukemia specialist Richard Larson, MD, professor of medicine at the University of Chicago and one of the prinicipal investigators in the initial trials of imatinib. "She opened a window that allowed us to see the genetic basis of the leukemias and other cancers."
Rowley's contributions to identifying chromosomal abnormalities in leukemias and lymphomas have changed the way these diseases are diagnosed and treated. Today, newer techniques can identify the DNA damage within individual cells, offering a much more precise diagnosis of disease and more effective treatments.
She continues to head an active laboratory at the University of Chicago Medical Center that focuses on the connections between genetic changes and cancer.