A ‘miracle’ drug for leukemia

In 1995, Melvin Mann, a major in the U.S. Army and the father of an 8-year-old daughter, was diagnosed with a rare and deadly blood cancer called chronic myelogenous leukemia. Unable to find a suitable bone marrow donor, he was told he had only a few years to live.

Three years later and barely able to get out of bed, Mann enrolled in a clinical trial testing an experimental drug called a tyrosine kinase inhibitor. “That was the drug that saved my life,” he recalls. Within 10 months of starting treatment, he had the strength to complete a marathon.

That “miracle” drug, eventually marketed as Gleevec (and known generically as imatinib), was the world’s first targeted therapy for chronic myelogenous leukemia and acute lymphoblastic leukemia and would become one of the most successful leukemia drugs in history. And much of the crucial research that led to Gleevec’s development was conducted by physician-scientist Dr. Owen Witte at UCLA with federal funding.

In the 1980s, Witte, a distinguished professor of microbiology, immunology and molecular genetics and founding director emeritus of UCLA’s Broad Stem Cell Research Center, found that a specific enzymatic activity in a cancer gene known as BCR-ABL played a role in certain types of leukemia.

That discovery defined a molecular target for these leukemias and helped usher in a new era of targeted cancer therapies — therapies that attack specific proteins, enzymes and genes that cancer cells need to grow and spread, while leaving healthy cells alone. In the case of chronic myelogenous leukemia, Gleevec inhibits the cancer-causing effects of a chemical called tyrosine kinase, a protein in the body that drives cell division.

Since then, Witte’s ongoing discoveries have helped to fundamentally reshape the treatment of leukemias, lymphomas and other cancers.

For Melvin Mann, Gleevec was a godsend. He was able to be there as his daughter got her driver’s license and graduated from high school, college and eventually medical school. And hundreds of thousands of chronic myelogenous leukemia patients worldwide — including the 9,000 diagnosed each year in the U.S. — have similar stories. After all, today they can expect to live long, healthy lives.

Witte acknowledges that he was one of many who contributed to the development of tyrosine kinase inhibitors — he and other scientists in academic and government labs across the country worked for decades, and federal funding for exploratory research powered their progress. The pharmaceutical industry now makes tyrosine kinase inhibitors for dozens of diseases, including other forms of cancer, autoimmune conditions and metabolic disease.

“Millions of people are taking these medicines and are walking around leading relatively normal lives, instead of getting sicker and dying,” Witte says. “And those pharmaceutical companies are keeping a lot of people employed and generating a lot of economic activity. I could not imagine a better use of federal funding than that.”