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The Evolution of Pharmacogenomics

A Chicago doctor and the science of personalizing drug dosing

By CORY FRANKLIN M.D.
   Developments in pharmacology and genetics, two scientific disciplines with a rich history since the 19th century, have been advancing at warp speed. In the 21st century, the confluence of those advances has produced a new medical discipline, pharmacogenomics, the science of personalizing drug dosing and treatment. Traditionally, most medicine dosages were simply taken from a book or standardized according to a patient’s body weight. Soon, pharmacogenomics will permit doctors to administer a patient’s medication based on that patient’s    specific DNA profile. Here in Chicago, one of the doctors at the forefront of this medical revolution is Dr. Mark Ratain, an oncologist and professor of medicine at the University of Chicago. He has been a   pioneer and leader in the field since its inception and has done some of the most innovative research. Recently, I asked Dr. Ratain about his work.
Dr. Ratain, give me a quick primer on what pharmacogenetics is.
   Pharmacogenetics is ascertaining how a person will respond to a particular medication by assessing that person’s genetic makeup. It tells us who to treat with a certain drug, who we shouldn’t treat and when we decide to treat someone, what dose is best. Essentially, it means the right drug at the right dose for the right patient.

What are the practical benefits of this?
   We want to determine how an individual's inherited DNA controls the ways they respond to medications—how they are absorbed,
distributed in the body, broken down and eliminated—and to use that knowledge to determine the optimum dose for each patient. We can identify a population at high risk of toxicity when they receive the standard dose of a drug so the dose can be reduced in those people. Likewise, we can identify a population with a low likelihood of
benefit at the standard dose so the dose can be raised to better effect.

Have you developed a specific pharmacogenomic test?
   We have developed a genetic test that determines which patients are likely to have a serious adverse reaction to irinotecan
hydrochloride, a key component of the standard first-line treatment for advanced colorectal cancer. Although most patients tolerate the drug quite well, some are genetically predisposed to severe side
effects from irinotecan treatment. The test enables us to know in
advance who is at risk. Those patients could be given reduced doses of irinotecan or another chemotherapy drug. Precise dosing is
extremely important for cancer chemotherapy because many drugs are most effective at the highest possible dose yet are also quite toxic. Finding the right dose is difficult because patients vary radically and unpredictably in their response to these drugs. From a cost standpoint, the test currently costs $700. The cost of treating endstage colorectal cancer currently approaches $200,000. Tailoring therapy could save a huge amount of money.

How can pharmacogenomics change our traditional approach to the patient?
   If we can do “batch genotyping,” where everyone gets DNA testing early in life, the medical information would provide lifetime benefits at a relatively low overall cost. It would ultimately provide more information than a single physician could manage. Linked to an electronic medical record with precise information technology, it would change how doctors approach patients. For instance, we might learn what cholesterol-lowering drug to prescribe to patients earlier in life. For a patient with pneumonia, the doctor would consider which drug to use and through pharmacogenetics, they would know whether it was the best drug for this particular patient. Used appropriately,
genetic information would change the questions we ask patients, how we examine them, what tests we order and what we prescribe.

Where do you see the field in a decade?
   I think we will be routinely genotyping patients. The costs will be low enough, and the information technology systems will be there to support it. The real question is, will doctors be prepared to use it? There will be controversies, and we will need studies with long-term patient follow-up. I emphasize long-term follow-up because in some cases the benefits patients accrue will occur over decades. I can’t say whether genotyping will be part of a patient’s standard health package or an add-on package, but it will definitely be part of medicine 10 years from now. At the University of Chicago, we have created the Center For Personal Therapeutics to study issues surrounding pharmacogenetics and the information technology involved.

Published: February 07, 2010
Issue: February 2010 Innovation Issue