March 15, 2007
New Pharmacy Professor Seeks to Match the Medicine to the Patient
Howard McLeod, PharmD, wants to help physicians get it right the first time when they select a medicine to treat cancer and other illnesses. He is heading a new research institute at the UNC School of Pharmacy that will find ways to match medicines to the unique makeup of the people needing them.
“In cancer and almost every other area of medicine, there are multiple drugs that work,” McLeod says. “But none of them work more than half the time. So when prescribers are faced with choosing what medicine to give a person, they often go with the drug they know best. And because there is often no way to know with great certainty how the drug may work in that individual, it may not be the one that will benefit the patient most.”
McLeod is the director of the new UNC Institute for Pharmacogenomics and Individualized Therapy, the first of its kind in the United States. The institute will work to create effective therapy and precise treatment options for individual patients suffering from a wide range of conditions. Initial efforts will focus on cancer therapy with planned expansion into cardiovascular disease, psychiatric disorders, and global health.
When a drug goes through clinical trials, its effectiveness and side effects are determined based on a large population. However, that information only tells individual patients what is possible. It does not tell them what their own experience is likely to be. There are dramatic differences among people in their reaction to a particular medicine, McLeod says.
“If individual patients knew they had twice the risk of a side effect as the average person, they could at least use that information to decide if the medicine is worth it to them or not,” he says.
In the near-term McLeod is less interested in perfection where everyone gets the best medicine 100 percent of time, but he expects to see incremental advancements that will improve health care in both the short and long run.
“When we talk about individualized therapy, we’re just talking about getting it right more often than we get it wrong,” he says. “The goal is not to hit a grand slam every time. It’s to get on base. And if we happen to get around to home, fantastic.”
For example, more than 2 million people in the US take the blood thinner warfarin. It is the textbook example of a drug with what pharmacists call a “narrow therapeutic index,” McLeod says.
“Give a little bit too much, and people bleed,” he says. “Give a too little, and they clot. You have to get it just right.”
There are entire clinics devoted to getting people on the right dose of warfarin, McLeod says. It is a roller coaster of trial and error before the right amount is identified. But based on new genetic discoveries, the Food and Drug Administration is issuing revised guidelines specifying that information present in two genes will affect the dose given to the patient. This is the third recent example where Dr McLeod has contributed to changes in the FDA treatment recommendations. “Progress is occurring; genetic information is improving the use of medicines in our lifetime.”
Howard McLeod, PharmD
Dr. Howard McLeod recently joined UNC as the Fred Eshelman Distinguished Professor of Pharmacy and professor of medicine. He is also a member of the Lineberger Comprehensive Cancer Center. He is an internationally recognized expert in the pharmacogenomic analysis of cancer treatments and comes to UNC from Washington University School of Medicine in St. Louis, MO. He is the author or coauthor of more than 260 scientific articles and is a member of the FDA Subcommittee on Clinical Pharmacology. He serves on the Scientific Program and Cancer Research Committees for the American Society for Clinical Oncology and is on the editorial board for seven scientific journals. Dr McLeod is a principal investigator in the National Institutes of Health Pharmacogenetics Research Network.
Pharmacogenomics is a new field exploring how the information in our genes influences our response to drugs. and involves the integration of knowledge of pharmacology with modern advances in genome analysis. Knowledge gained this way is changing the use of many anticancer agents by enabling scientists to identify patients who are at risk for adverse reactions or those who are likely to benefit from a particular treatment.
Dr. McLeod is currently working with the large national clinical trials groups—such as Cancer and Leukemia Group B—to confirm that findings from small institutional studies will actually translate into better therapy across the nation. Most large CALGB studies now collect a specific blood sample for DNA analysis as part of the trial.
He and colleagues have already identified specific genetic components of several drugs that have lead to the FDA changing the drug package inserts to identify patient groups that are genetically predisposed to risk of severe side effects or inadequate benefit. This has included drugs used to treat advanced colorectal cancer (Irinotecan), solid tumors (5-FU) and childhood leukemias (thiopurines such as mercaptopurine).
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