2003 - Curing cancer is Dr. Brian Druker’s only business, and he has reached a significant milestone: He helped get a revolutionary type of cancer drug onto the market and into the hands of patients suffering from chronic mylogenous leukemia (CML). Unlike traditional chemotherapy, the new drug, marketed as Gleevec, targets the genetic abnormality that causes the cancer and leaves healthy cells alone, thereby causing far fewer side effects.
The drug’s approval by the U.S. Food and Drug Administration (FDA) in June 2001 prompted intense media coverage, and some observers hailed Gleevec as a possible cure for CML. Many patients have achieved complete remission of the disease while on the drug. Consequently, Dr. Druker found himself in the media’s high beams.
Brian Druker was instrumental in getting the new leukemia drug, Gleevec, onto the market and into the hands of patients suffering from chronic mylogenous leukemia (CML). The drug has proved effective in fighting the genetic abnormality that causes CML.Dr. Druker, a 2000 BWF Clinical Scientist Awardee in Translational Research, has received numerous awards and accolades for his work but is modest about all the hoopla. “I always tried to focus on what this meant for cancer research,” he says, “not only hope for CML patients, but hope for everyone.” Dr. Druker believes, and is devoting his career to the belief, that understanding the molecular basis for a disease can lead to specific and effective treatment.
“This discovery validated years and years of research and the efforts of hundreds, if not thousands, of researchers,” he adds. “If talking about this achievement can translate into more funding and more research and discoveries, then the media coverage was being put to good use.”
Dr. Druker became interested in leukemia during medical school at the University of California–San Diego. “During my first year, I took an elective class where we learned about the history of chemotherapy,” he recalls. “In the 1940s and ‘50s, it was common for new treatments to be tested in children. Acute lymphoblastic leukemia (ALL) is the commonest form of childhood bone marrow cancer, and children suffering from ALL would die within weeks. Then treatment began to include methotrexate and prednisone and these drugs doubled the survival rate. In the course of 20 years, this type of leukemia became curable.”
Fascinated by the scientific achievement of moving a disease from being fatal to curable, Dr. Druker says he felt that medicine was nevertheless using a harsh therapy to achieve results. “There had to be a better way,” he says. “And that’s what sparked my interest in cancer research.”
After medical school, a residency in internal medicine at Washington University’s Barnes Hospital, and a clinical oncology fellowship at Dana-Farber Cancer Institute, Dr. Druker decided he needed to get basic lab training. “Cancer treatment then was still chemotherapy and surgery-based and non-targeted,” he says. “Though chemotherapy had come a long way, we still didn’t have a precise understanding of how and why it worked, and it still had lots of toxicity. We needed to understand cancer at the molecular level in order to make inroads.”
Dr. Druker recalls that it was Dr. David Kipnis, currently outgoing chair of the BWF Board of Directors and then chair of medicine at Barnes, who suggested that he pursue his career in the emerging field of oncogenes. “He was absolutely right,” says Dr. Druker, who then began working in the lab of Dr. Thomas Roberts—one of the world’s leading experts on tyrosine kinases—at Dana-Farber. Tyrosine kinases are proteins that control cell growth and can trigger the wild proliferation of white blood cells seen in CML. While there, Dr. Druker also collaborated with leukemia expert Dr. James Griffin on signaling in white blood cells.
In 1993, Dr. Druker moved to the Oregon Health & Science University and set up his own lab. By that time, he was already working on CML and things were about to snowball. Scientists from the drug company Novartis (then Ciba-Geigy) approached Dr. Roberts at Dana-Farber about setting up a drug discovery program to inhibit tyrosine kinases, because such a drug would be useful in treating cancer and other diseases. “Since I had been the only oncologist in Dr. Robert’s lab, it was natural for the Novartis scientists to get my opinion about what the potential therapeutic targets would be in the field of tyrosine kinases,” Dr. Druker recalls. “I thought CML would be one of the first diseases that would be treated [with a kinase inhibitor].”
Convincing the drug company to develop an inhibitor specifically targeting CML was another matter, but Dr. Druker says he was ultimately able to persuade the drug maker that getting a CML drug into the market would make the compound available as a possible treatment for other cancers. It was only a matter of time before Gleevec was developed, entered into clinical trials and, after showing such promise in treating CML, fast-tracked for FDA approval.
One of the key issues Dr. Druker is still grappling with is whether he and others can cure CML. “I think Gleevec is one of the major building blocks to get there,” he says.
Dr. Druker’s focus now is on improving upon Gleevec as a single agent. “I still want to do better than 80 percent of CML patients alive and well in 10 years,” he emphasizes. “I want to see 80 percent cured.”
He is also scrutinizing how CML becomes resistant to Gleevec and says he and others are learning that the cancer mutates to evade Gleevec’s attack. “We’re working with drug companies to develop new inhibitors,” he says. “We’re also trying to predict how people will do in treatment. If we think someone has the potential to become resistant, we want to know that as soon as possible so we can intervene as soon as possible.”
Dr. Druker says he also is looking at other targets in other cancers, particularly a similar target in acute myeloid leukemia that has also been identified by other research groups. “Four different drug companies are working on new inhibitors for this target,” Dr. Druker says. “Because of Gleevec’s success, people believe in the new paradigm and are willing to commit to it now. What’s exciting is that as we identify more and more targets for therapy, it’s just a matter of coming up with the right compound to modulate that target.”
Aside from his dedication to cancer research, Dr. Druker’s other passion is running. He’s qualified for the spring 2003 Boston Marathon but can’t run because he and his wife are expecting the birth of a baby at roughly the same time. Characteristically, Dr. Druker is not deterred. He’s planning on running another qualifying marathon and tackling Boston in 2004.
When asked about juggling work and family, Dr. Druker says, “Now that I’ve achieved a modicum of success, I can spend more time focusing on my family; I can accomplish my research with people working for me and with me; and I can leverage my success into success for other people.”
A Conversation With Brian J. Druker, M.D. Researcher Behind the Drug Gleevec
The New York Times (2 November 2009)