CML Experts - Chronic Myeloid Leukemia
''The story of Gleevec began in 1960, when scientists at the University of Pennsylvania (Dr. Peter C. Nowell and Dr. David E. Hungerford) noticed that one chromosome in the blood cells of many CML patients was shorter than normal - it was missing a big chunk of its DNA. The stubby chromosome was nicknamed "the Philadelphia chromosome" and marked the first time that a chromosomal defect was linked to cancer.
Scientists now had a tantalizing clue, but they didn't yet have the tools needed to use the clue to solve the mystery of CML. Another clue was revealed thirteen years later (1973), when a researcher at the University of Chicago ( Dr Janet Rowley ) discovered that the missing end of the short chromosome had moved and fused with another chromosome. By the 1980s, scientists were able to use genetic mapping to show that the two ends of the broken chromosomes produced a cancer-causing protein, known as Bcr-Abl.
In early 1990, Dr. Elisabeth Buchdunger and Dr. Juerg Zimmerman, both of Novartis, accepted a challenge from the leaders of the tyrosine kinase inhibition team - Nick Lydon and Alex Matter: Refine the lead compound that blocks the enzyme that triggers chronic myeloid leukemia (CML) without harming other members of the same family, called kinases, that are needed for the body to function. Two years and some 400 molecules later, the researchers and their colleagues came up with the molecule that became Gleevec®, a medicine that is helping many patients with this debilitating and usually fatal disease and giving hope to patients with other cancers.''
Extract of The Story of Gleevec by Innovation.org
"" In the 1990s Dr. Brian Druker began looking for the abnormalities in cancer cell growth and specifically at the effect of enzyme inhibitors in animal models of cancer. His work led him to an enzyme that cancer cells seemed addicted to (tyrosine kinase). He thought that inhibiting the enzyme might inhibit the runaway cell growth of the cancer cells.
He then approached Nicholas Lydon, of Ciba-Geigy, a pharmaceutical company. Lydon specialized in tyrosine kinase inhibitors. Working together they were able to identify the drug, Gleevec, as a compound which might kill CML leukemia cells but leave healthy cells alone. After many studies, they convinced the drug company Novartis (which Ciba-Geigy had become after a merger) to put the drug into a human clinical trial. This was not an easy corporate decision. Clinical trials are very expensive, and because CML is a rare disease, it was possible that Gleevec would be unprofitable, even if successful.
Still, Novartis did decide to proceed and in June, 1998, a clinical trial began using the drug. Within 6 months, a most remarkable thing happened. Most clinical trials of new cancer drugs measure success if the drug extends the life of a small percentage of patients by a few months. For Gleevec, 53 out of 54 patients achieved remission – their white blood cells counts became normal. Plus, there were few side effects! ""
Extract of Brian Druker by ScienceHeroes.com
See also the History of Gleevec