Brian J. Druker, M.D. and Charles L. Sawyers, M.D. are the 2011 recipients of the American Society for Clinical Investigation's Stanley J. Korsmeyer Award, in recognition of their contributions to the development of novel therapeutics in the treatment of leukemia and other forms of cancer. Their work, collaboratively and as individuals, has revolutionized the treatment of cancer, providing an inspiring model for the transformation of clinical medicine through rigorous molecular science.
Drs. Druker and Sawyers will share the $10,000 Award honorarium and present the Korsmeyer Award Lecture at the 2011 ASCI/AAP Meeting (April 15-17, in Chicago, Illinois). This is the first time that the Award has been shared.
The breakthrough development of tyrosine kinase inhibitors to arrest chronic-phase chronic myeloid leukemia (CML) is a case study in the successful progress of basic research to the clinic. The discovery, in the early 1960s, of a chromosomal abnormality (known as the Philadelphia chromosome) in a majority of CML patients presented a potential treatment target — the abnormality produced an active tyrosine kinase that fed cancer growth. However, the standard treatment remained chemotherapy, with its attendant toxic effects.
In the mid 1980s, Dr. Druker began his lab work investigating the genetic abnormalities that drive cancer. Among his early successes was developing a laboratory reagent to help identify drugs that inhibit cancer cell growth. As an extension of that work, in 1993 he began collaborating with a pharmaceutical company to test compounds that could stop CML cells from growing without harming normal cells. Of the compounds he tested, Dr. Druker identified imatinib, a tyrosine kinase inhibitor, as the most effective. After extensive laboratory studies, Dr. Druker was able to move the drug into clinical trials in 1998.
Working with industry, Drs. Druker and Sawyers in 1998 began clinical trials of imatinib, demonstrating in populations of chronic-phase CML patients such impressive results — restoration of white blood cell counts to near normal and with only minimal side effects — that the Food and Drug Administration approved the drug in 2001, in just under three years.
It became clear in the course of the trials that problems remained for some CML patients, who developed resistance to imatinib, leading to relapse and acceleration of the disease. In 2001, Dr. Sawyers and his lab identified an assortment of mutations that caused resistance to imatinib and, working with structural biologist John Kuriyan, recognized that other kinase inhibitors could block growth of the resistant tumor cells. These findings led to the development and FDA-approved use of other tyrosine kinase inhibitors in patients with resistant CML. Imatinib is now approved for use in other diseases such as gastrointestinal stromal tumor (GIST), and several other kinase inhibitors have been developed to target other cancers following similar molecular principles.
Dr. Druker is the director of the Oregon Health & Science University Knight Cancer Institute, associate dean for oncology in the OHSU School of Medicine, adjunct professor in the Department of Pediatrics: Division of Hematology and Oncology, JELD-WEN Chair of Leukemia Research at OHSU, and a Howard Hughes Medical Institute investigator. He was elected to the American Society for Clinical Investigation in 1997.
Dr. Sawyers is an investigator of the Howard Hughes Medical Institute at Memorial Sloan-Kettering Cancer Center, where he is director of the Human Oncology and Pathogenesis Program and holds the Marie-Josée and Henry R. Kravis Chair. He is a member of the National Academy of Sciences and the Institute of Medicine of the National Academies. He was elected to the American Society for Clinical Investigation in 1999.
Drs. Druker and Sawyers shared the 2009 Lasker-DeBakey Clinical Medical Research Award with Nicholas B. Lydon.