Making Oncology History: Imatinib Pioneer Created His Own Opportunities

Beth Fand Incollingo
Published Online: Thursday, January 17, 2013
Dr. Brian J. Druker Brian J. Druker, MD
There are lessons to be learned from interacting with cancer patients, and⎯luckily for the oncology community⎯Brian J. Druker almost missed the most important one.

“If you take care of cancer patients, what you should learn is that you need to make the most out of every day, to live life to its fullest,” said Druker, MD, director of the Knight Cancer Institute at Oregon Health & Science University (OHSU) in Portland. “If I developed cancer and all I did was work hard, that doesn’t seem like a very fulfilling life.”

During the early years of his career, though, it never occurred to Druker to adopt that perspective. Instead, the endless frustration of treating patients he couldn’t cure—or sometimes even help— drove the physician into the lab to work tirelessly at developing new therapies.

As it turned out, it was fortunate for the oncology community that he did. A dozen years ago, Druker’s efforts led to the development of imatinib (Gleevec), an oral tyrosine kinase inhibitor (TKI) initially indicated for patients with chronic myeloid leukemia (CML) that has proved to be one of the earliest and most successful targeted therapies in the oncology armamentarium.

In one trial that helped pave the way for the drug, Druker and colleagues found that imatinib restored normal blood counts in 53 out of 54 interferon-resistant CML patients, a response rate rarely seen in cancer with a single agent (N Engl J Med. 2001;344[14]:1031-1037). Fifty-one of the patients were still doing well after a year on the medicine, and most reported few side effects, according to the National Cancer Institute (NCI) (http://goo.gl/RmIH5).

Imatinib was groundbreaking not just because of those results, but also because of how it generated them. While previously approved molecular-targeting drugs interfered with proteins associated with cancers, imatinib was the first to directly turn off the signal of a protein known to cause a cancer, according to the NCI. The drug was approved in May 2001, with phase II trials still in progress and after an FDA review of less than three months, still an all-time speed record.

Today, patients with CML who take imatinib are projected to survive an average of 30 years, Druker said, a far cry from the three- to five-year prognosis that was standard when he began practicing medicine in the 1980s. And, imatinib has been approved for the treatment of additional tumor types, including Philadelphia chromosome-positive acute lymphoblastic leukemia and KIT (CD117)-positive gastrointestinal stromal tumors.

On a broader scope, the insights that led to the development of the drug have helped lay the groundwork for the creation, by other labs, of several approved treatments for imatinib-resistant CML, and also of targeted therapies for other cancers, including the kinase inhibitors vemurafenib, erlotinib, gefitinib, and crizotinib.

All those developments make Druker glad that he gave the decade of his life from his mid-30s to his mid-40s almost exclusively to research, living a solitary life and working 16-hour days.

“Because of what I did and the sacrifices I made,” the 57-year-old said, “I got to see patients who benefited from a treatment I helped develop, and got to give them hope when they had no hope. That’s a gift that can’t be replaced by anything else.”

Continuing the Fight

In the years since imatinib’s approval, Druker has maintained his focus on finding new and better treatments for CML and other leukemias. In particular, he’s seeking ways to beat the resistance to imatinib that arises in about 15% of patients with CML within five years of beginning treatment.

While there are already three TKIs on the market for refractory CML, including bosutinib (Bosulif), approved this fall, “there’s still one mutation that none of those drugs will shut down—T315I,” Druker said.

“We worked for close to six years testing drugs that Ariad designed until we identified one that shut this down,” said Druker, referring to the Cambridge, Massachusetts, pharmaceutical company. “The drug, ponatinib, works incredibly well against that mutation and also across the board in CML, and has made it through clinical trials.” In December, the FDA approved ponatinib, three months ahead of schedule Find out more.

Druker spends a fair amount of time conducting such research in his 16-person lab at OHSU, a hilltop institution that overlooks downtown Portland.

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