OHSU Scientists Begin Human Trials Of A Drug Aimed At The Underlying Cause Of Chronic Myelogenous Leukemia

r or leukemia unless you understand what makes these mutant cells behave in the way they do," explained Grover Bagby, M.D., director of the Oregon Cancer Center. "Second, cancer and leukemia cells behave in an abnormal way because the structure of cellular proteins has been altered by mutations. Although this new agent needs to be validated in large numbers of patients, Dr. Druker's work is the perfect example of the power of molecular biology to bring new, more effective and potentially less toxic treatments to patients with serious illnesses. We need such highly targeted approaches for all patients with malignant diseases."

Hitting its victims in mid-life, CML arises when chromosomes 9 and 22 exchange segments and form a faulty gene that produces an abnormal protein called BCR-ABL. BCR-ABL is a protein belonging to a family of enzymes called tyrosine kinases that influence the control of cell growth. The abnormal BCR-ABL protein increases the enzymatic activity that drives the white cells to proliferate uncontrollably, inducing leukemia. Essentially, there are no brakes to stop the proliferation.

The investigational drug inhibits the enzymatic activity of the renegade BCR-ABL protein. Called a tyrosine kinase inhibitor, the drug has succeeded in destroying BCR-ABL cells in cell culture studies and animal trials in mice, but it does not kill normal cells. "We will treat CML patients with this compound in the form of a pill," said Druker. "We hope the compound will seek out the faulty cells with the BCR-ABL protein and destroy them."

"The highly specific drug therapy is a direct extension of our lab work on CML," said Druker. "Our studies have revealed that the BCR-ABL protein is the obvious abnormality to attack in CML."

Druker stressed that the development of this new cancer- fighting drug represents an example of the fundamental importance of determining the molecular mechanisms that drive cell growth in specific disea

Contact: Henry Sessions
Oregon Health & Science University

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