HomeOur ScientistsBrian J. Druker

Our Scientists

Brian J. Druker, MD
Investigator / 2002–Present

Scientific Discipline

Cancer Biology, Medicine and Translational Research

Host Institution

Oregon Health & Science University

Current Position

Dr. Druker is also JELD-WEN Chair of Leukemia Research and a professor of medicine at the Oregon Health & Science University Cancer Institute.

Current Research

Mechanism-Based Therapy for Leukemia

Brian Druker is interested in translating the knowledge of the molecular pathogenesis of cancer into specific therapies and investigating the optimal use of these molecularly targeted agents.

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A functional genomics approach to targeted therapies for leukemia...

Biography

Chronic myeloid leukemia (CML) can be traced to a single genetic event—the swap of pieces of DNA between two chromosomes. This rearrangement produces a faulty signaling protein that triggers white blood cells to divide incessantly.…

Chronic myeloid leukemia (CML) can be traced to a single genetic event—the swap of pieces of DNA between two chromosomes. This rearrangement produces a faulty signaling protein that triggers white blood cells to divide incessantly. Oncologist Brian Druker has revolutionized the treatment of cancer through research to develop Gleevec, the first drug to target the genetic defects of a particular cancer while leaving healthy cells unharmed. Based on his studies, Gleevec is now the treatment of choice for patients with CML, and its success has opened the door to developing targeted therapies for other cancers.

More than a decade ago, Druker identified STI571, the precursor to Gleevec, as a promising anticancer compound for its ability to kill CML cells by turning off the signal of the abnormal cancer-causing protein. He also conducted the first clinical studies of Gleevec, demonstrating that the drug could effectively return blood cell counts to normal in CML patients, with only minor side effects. Druker is currently focused on developing more effective treatments for patients whose leukemia eventually recurs while taking Gleevec. He ultimately hopes to identify other molecular targets in leukemia and develop drugs that block these defects.

After earning his medical degree and completing an oncology fellowship, Druker worked as an instructor and researcher at Harvard. He spent most of his laboratory time studying a large family of signaling proteins called tyrosine kinases and exploring their link to human disease. He also developed tools to detect the activity of tyrosine kinases, an accomplishment that proved crucial to the identification of Gleevec. Druker eventually chose to focus his work on CML because it was known to be caused by an overactive tyrosine kinase, BCR-ABL, which is produced by the exchange of genetic material between chromosomes 9 and 22. But after several years of investigating this connection, Druker was restless; although he found lab work fascinating, he felt too far removed from the people he was supposed to be helping. He began treating patients in a community cancer clinic half a day a week—an experience that cemented his desire to develop targeted drugs to attack cancer cells without the harmful side effects of chemotherapy. "For me, the connection to cancer patients has been a driving force in my career," Druker says. "They compelled me to work harder and faster and to be their advocate for new and better therapies."

Druker moved on to Oregon Health & Science University in 1993, where he focused on treating leukemia patients and on finding an inhibitor for BCR-ABL. At that time, CML patients had two main treatment options: bone marrow transplant, which carries high risks, or daily injections of interferon, which often result in side effects similar to a severe case of flu. The drug maker Novartis was already synthesizing various inhibitors of protein kinases using the tools that Druker had developed in his laboratory, and he obtained several to evaluate against leukemia cells. He found that one drug—Gleevec—inhibited cancerous white blood cells without affecting healthy human cells, but Novartis was initially reluctant to develop it for CML, a disease that strikes only 5,000 people in the United States annually. Druker persisted, and Novartis eventually produced enough Gleevec for him to evaluate in patients.

A phase I clinical trial began in June 1998, and within six months remissions had occurred in all patients, as determined by their white blood cell counts returning to normal. This result was considered nothing less than remarkable for patients with terminal cancer who had exhausted all other treatment options. Clinical trials were soon expanded to include other patients with CML, and results were similarly stunning. Today, the average five-year survival for CML patients who take Gleevec is close to 90 percent. "What this tells us is that the disease is critically dependent on the BCR-ABL kinase, and by shutting down this critical driving force for leukemia, we can have a major impact on the disease," Druker explains.

Druker's current research projects are aimed at learning why each year some 4 percent of newly diagnosed patients with CML develop resistance to Gleevec and why most patients on the drug have minute levels of cancer that linger even after treatment ends. Resistance to Gleevec most commonly results from mutations in the BCR-ABL kinase that reactivates its signaling mechanism. He recently identified a class of compounds that can inhibit most of these mutants, and similar compounds are now in clinical trials. A more pressing problem, Druker believes, are the traces of leukemia that remain in patients' bodies, a phenomenon called molecular persistence. He is working in the laboratory to purify leukemia cells from patients to determine why these cells aren't being killed so that a strategy can be developed to eradicate the cancer.

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Education

  • BA, chemistry, University of California, San Diego
  • MD, University of California, San Diego

Awards

  • Lasker-Debakey Clinical Medical Research Award, 2009
  • Japan Prize, Japan Prize Foundation
  • Robert Koch Prize
  • Richard and Hinda Rosenthal Award, American Association for Cancer Research
  • Warren Alpert Prize, Harvard Medical School
  • Dameshek Prize, American Society of Hermatology
  • Karnofsky Award, American Society of Clinical Oncology
  • Kettering Prize, General Motors Cancer Research Foundation
  • Stanley J. Korsmeyer Award, American Society for Clinical Investigation
  • Ernest Beutler Lecture and Prize, American Society of Hematology
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Memberships

  • Institute of Medicine of the National Academies
  • American Association of Physicians
  • National Academy of Sciences
  • American Academy of Arts and Sciences
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