A magic pill?

Aug 20 2007 Published by under Medicine

This is the story of a real magic pill.  Well, maybe not magic per se, but a pill that successfully treats some cancers that previously were uniformly deadly.

It starts back in 1960. A couple of researches at the University of Pennsylvania were looking at chromosomes in the blood cells of patients with chronic myelogenous leukemia (CML), and one stood out. This unusal chromosome was named the "Philadelphia chromosome". In 1973, another researcher was able to piece together the precise genetic defect that creates the Philadelphia chromosome. In 1998, Peter Nowell, one of the chromosome's discoverers, and Janet Rowley, the later scientist who discovered the exact defect, were awarded the Lasker Award for their work.

The significance of this work is that a particular chromosomal defect was associated with a particular cancer for the first time. This not only allowed for increased understanding of how cancers work, but also opened the door on how to fight them.
CML isn't terribly common--it probably kills about 500 people per year in the U.S. But these numbers hide an amazing success story. Back to the science, and a little background in biology.

Chromosomes are large clumps of DNA (and protein), and the strings of DNA in them are instructions for making proteins. We call these instructions "genes". These proteins are the structural and functional components of our bodies, and include enzymes that control when cells will or will not divide. Cells that divide in an uncontrolled way become cancers, so the start and stop mechanisms for these proteins are quite important. Control mechanisms exist on several levels. Sometimes they control when a gene will and will not make a protein, sometimes they determine when a protein will or will not function. A problem with any of these mechanisms can be quite bad.

The Philadelphia chromosome is a problem. It contains a gene called "BCR-abl" which produces a protein called a "tyrosine kinase" (TK). This particular TK is not present in normal cells. When it is present in certain white blood cells, it is stuck in the "on" position, and causes a cell to keep dividing in an uncontrolled manner. These abnormal white blood cells keep dividing, producing the condition we call "leukemia" ("white blood").

In the 20th century, the 5-year survival rate for CML was somewhere between 32-50%, and didn't improve much. Then this guy named Drucker came along.

Brian Drucker is a doctor and researcher who happened to be interested in TKs. He helped figure out how the Philadephia chromosome caused these white blood cells to turn cancerous. He teamed up with a drug company (which eventually became Novartis), to develop a compound that would inhibit the TK that was stuck on in CML.

Most cancer therapies traditionally were "cytotoxins", that is, they killed cells. This is good---they killed cancer cells. But they also killed normal cells, giving chemotherapy a bad reputaion as a miserable thing to go through. If a compound could be found that turned off only this one little protein that caused CML, it had the potential to stop the disease without hurting healthy cells.
In the late 90's, they found it. It was called STI-571, and not only did it seem to turn off the TK enzyme, it also came in a pill.
It went through the usual phases of clinical studies. I remember as a medical resident on a busy cancer ward one of my professors working hard to get access to this as yet unproven drug, as it seemed so promising. Patients were scrambling to enter research trials.
Well, the trials are done. Reported at the end of 2006, the 5-year survival rates for CML patients taking Gleevec (the commercial name for STI-571) is about 90%.  That is a remarkable number, and some CML patients are now dying of other diseases rather than their cancer.

This is an incredible story. It follows almost 50 years of hard and brilliant work by many researches named and unnamed, as they discover the cause of a disease, and it's treatment.

It stands in stark contrast to the promises of the "alternative medicine" crowd. They proclaim loudly, "Buy my book! Take my enemas! Infuse my vitamins! I will cure you!" Of course, they cure no one, because they are lazy. They don't understand science, and don't care to. They prey on fears and hopes, and don't deliver. They should be ashamed.

The rest of us can be proud and hopeful as medicine learns from it's successes and failures, and marches on.

References (not otherwise linked above):

Brian J. Druker, M.D., François Guilhot, M.D., Stephen G. O'Brien, M.D., Ph.D., et al for the IRIS Investigators. Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia. NEJM Volume 355(23):2408-2417, December 7, 2006. http://content.nejm.org/cgi/content/full/355/23/2408

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