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Cancer Research: It's About Time

Friday, March 16, 2012

Written by William C. Phelps, PhD, director of preclinical and translational cancer research, American Cancer Society, December 14, 2011

In the 1960s two young scientists in Philadelphia, Dr. Peter Nowell from the University of Pennsylvania and Dr. David Hungerford from Fox Chase Cancer Center, spent their days peering through microscopes at white blood cells. They noticed that when they stained cells from patients with chronic myeloid leukemia (aka chronic myelogenous leukemia, or CML), they would very often see an odd, minute chromosome in addition to the normal set.

We know today that this was a landmark observation. Dr. Nowell and Dr. Hungerford named their discovery the “Philadelphia Chromosome” in keeping with the tradition of the day, and it soon became an important way to diagnose CML.

In the 1970s, Dr. Janet Rowley at the University of Chicago used newly-developed techniques that highlighted different regions of chromosomes to look more carefully at the Philadelphia Chromosome. She determined that they looked odd because two large pieces of two different chromosomes had changed places. But the significance of that translocation wasn’t immediately apparent.

At the Massachusetts Institute of Technology in the 1980s, Nobel Laureate Dr. David Baltimore followed up on Dr. Rowley’s observations to make a critical discovery about what causes CML. His laboratory was able to show that one of the results of the exchange of chromosomal material was the creation of a completely new gene, BCR-Abl, which was only found in CML cells. Dr. Baltimore went on to show that the BCR-Abl protein causes CML in laboratory and animal models. Knowing what causes CML provided the platform for the next major discovery in the treatment of this form of leukemia, which is most commonly found in older adults.

Dr. Brian Druker at Oregon Health and Science University combined perseverance, innovation, and personal commitment to cancer patients to make the next major breakthrough in the 1990s. One of the most critical challenges that he faced was not scientific, but economic.

At the time, the number of patients afflicted with CML in the U.S. was thought to be too small to entice major pharmaceutical companies to develop a drug. Regardless, Dr. Druker was able to convince Novartis (then called Ciba-Geigy) to allow him to screen some of the compounds in their huge chemical collections. Remarkably, he discovered a drug that blocked the activity of the BCR-Abl protein.

After another decade of testing and clinical trials,  Gleevec (imatinib mesylate) was approved by the Food and Drug Administration for treatment of CML in 2001. Together with other, later drugs which target the BCR-Abl protein, Gleevec has transformed CML from a lethal diagnosis to a manageable disease for more than 90 percent of patients.

Effective treatment of CML has undoubtedly saved thousands of lives, but it took four decades of discovery in four different parts of the country to make this possible. No matter how much we want a cure for cancer tomorrow, the history of science has taught us that it takes time. Even a brief examination of the major breakthroughs in cancer medicine reveals that the major discoveries were only possible because of a series of advances, painstakingly accumulated over many decades.

In every case, success results from the marriage of hard work and innovation nurtured by the element of time. (Money is crucial, too, of course. Without it, research can’t happen at all, and cutting funding only slows the development of new treatments.)

Discoveries made in the 1990s set the stage for the advances in targeted therapies against a broad range of cancers, including melanoma, lung cancer, and leukemia, for which we’ve seen major advancements during just the past year. These promising paths need the time — and dollars, of course — to find their greatest benefits for cancer patients during the next decade. It really is about time.

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