Acclaim for a precision oncology pioneer in Oregon

Like few other drugs in the history of oncology, Gleevec transformed the outlook for patients: a disease with a life expectancy of less than five years – chronic myeloid leukemia – became a manageable condition with a life expectancy almost equal to that of the general population. The drug, shepherded from laboratory to clinical success by Brian Druker, M.D., resoundingly affirmed the premise that understanding the earliest drivers of cancer formation can lead to less toxic and more effective treatments.

Photo: Brian Druker, M.D., director of the OHSU Knight Cancer Institute in Portland, Oregon (OHSU/Kristyna Wentz-Graff)In recognition of this work, Druker has been awarded the 2018 Tang Prize in Biopharmaceutical Science, along with Tony Hunter Ph.D., Professor of Biology at the Salk Institute, and John Mendelsohn, M.D., President Emeritus at the University of Texas MD Anderson Cancer Center. Each of the three made discoveries that led to successful targeted cancer therapies, and will equally share a cash prize of approximately $1.33 million and a grant of up to $333,000.

“This award represents hope for patients and their families, and reminds us that we can create effective and non-toxic therapies,” Druker said in a news release. “Our team will continue to help advance science so that, one day, what we have seen with Gleevec will be possible for all patients with cancer.”

Gleevec quickly became the gold standard for first-line treatment of chronic myeloid leukemia in 2001, when the drug received approval by the U.S. Food and Drug Administration. It is a tyrosine kinase inhibitor that specifically targets a mutant protein, BCR-ABL1, that is a driver of malignant transformation in the chronic myeloid leukemia, or CML. Second- and third-generation tyrosine kinase inhibitors have continued to better outcomes by providing effective therapy when CML develops resistance to Gleevec.

The targeted drugs have also allowed for the successful stopping of therapy in a subset of patients. Druker and colleagues have estimated that approximately 10 percent of Gleevec-treated patients might be able to achieve a stable treatment-free remission. They say that second-generation agents may enable an even larger proportion of patients to be eligible to attempt treatment-free remission.

Other cancers haven’t been as amenable to the targeted therapy approach because the genetic alterations driving them are more complex than the BCR-ABL1 mutation that underlies CML. Solid tumors, for instance, tend to quickly develop resistance to targeted therapies by diverting to alternative metabolic and signaling pathways.

Nevertheless, the imatinib experience has “fundamentally altered the field of oncology,” in the words of Dan L. Longo, M.D., a deputy editor of the New England Journal of Medicine. While none of the new targeted therapies appears to cure a majority of patients, and many hurdles remain, he said, “The future of oncology is more hopeful now.”

The Tang Prizes will be presented at a ceremony on Sept. 21 in Taiwan. Laureates are selected on the basis of the originality of their work along with their contributions to society. Nomination and selection is conducted by an independently acting selection committee composed of accomplished scholars from around the world.

Read more about the award at OHSU News.

Years of life expectancy at age 55 for people diagnosed with CML compared with the general population, from the work of Bower et al. (OHSU/Joe Rojas-Burke)

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