Cancer Drug Gleevec Wins Lasker Award

The shortened "Philadelphia chromosome" seen in certain leukemias (picture from nature.com)

The shortened "Philadelphia chromosome" seen in certain leukemias (picture from nature.com)

The big science news of the day was the announcement of the Lasker Awards, informally thought of as the American version of the Nobel Prize for physiology and medicine. This year’s clinical medical research award went to a trio of researchers from Oregon Health & Science University, Sloan-Kettering Cancer Center and drug company Novartis, but you could just as easily say it was awarded to a drug: the cancer treatment Gleevec. And Gleevec’s roots stretch back to the campus of the University of Chicago and a very familiar face on this blog: Janet Rowley.

This year, Rowley has already received the Presidential Medal of Freedom, the Gruber Genetics Prize and stood at President Obama’s shoulder as he repealed federal limitations on stem cell research. Oh, and she’s already won the Lasker Award herself, in 1998. So it’s okay that she’s not mentioned among today’s winners.

As with most stories of scientific discovery moving from the laboratory bench to the pharmacy, it’s simplistic to pin the achievement on one, three, or even ten people. The path to Gleevec’s discovery go back beyond Rowley to the 1950’s when Peter Nowell and David Hungerford – working at the University of Pennsylvania in Philadelphia – found an odd, shortened chromosome in patients with a form of cancer called chronic myelogenous leukemia (CML). They called that stubby piece of DNA, appropriately enough, the Philadelphia chromosome.

But debate raged among cancer researchers over whether the Philadelphia chromosome was the cause of CML or a symptom of the cancer. It wasn’t until more than a decade later that Janet Rowley, analyzing pictures of chromosomes on the dining room table of her Hyde Park home, discovered that the Philadelphia chromosome is the result of a chromosomal translocation, where a piece of one chromosome is transferred to another.

From there, researchers set out to find the exact genes that are misplaced in the translocation that causes CML. Another decade passed before the culprit was identified – the abl gene, a cancer-causing gene discovered in 1969 by Herbert Abelson, who later became chair of pediatrics at the University of Chicago Medical Center. When the translocation occurs, the abl gene is grafted to a gene called bcr, activating a cellular protein called tyrosine kinase that causes uncontrolled white blood cell proliferation, the defect at the heart of CML.

Even after the mechanism was identified, someone still had to develop a drug to inhibit tyrosine kinase activation, and it took another decade before clinical trials of that drug, known originally as imatinib, could take place in CML patients. But unlike most clinical trials, the research was immediately decisive about imatinib’s effectiveness, as 53 of the 54 patients enrolled in the original trial exhibited remission of their cancer. Now sold as Gleevec, the drug has become a staple of cancer treatment around the world, and continues to impress with it’s high success rate in treating CML patients. According to one study, the five year survival rate for CML patients before Gleevac was 30%. The survival rate for patients on Gleevec? 89%. The drug has also been found useful in certain gastrointestinal cancers, and is currently being studied as a treatment for stroke and diabetes.

So congratulations to Brian Druker, Nicholas Lydon and Charles Sawyers, who will share a $250,000 award in addition to the admiration and appreciation of their colleagues. And congratulations to Janet Rowley and Herbert Abelson, University of Chicago researchers who added important pieces to the scientific mosaic that was the discovery of a life-saving drug.

(Here’s a 2001 article from the University of Chicago Magazine on Rowley and Abelson’s contributions to the development of Gleevec, and an excellent summary of Gleevec’s history and mechanism from Nature.)

About Rob Mitchum (526 Articles)

Rob Mitchum is communications manager at the Computation Institute, a joint initiative between The University of Chicago and Argonne National Laboratory.

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