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Children suffering from catastrophic diseases face additional challenges once they enter treatment. Some young patients suffer unexpected harsh, adverse reactions to therapeutic drugs; other children may undergo months of therapy that weakens them and makes them feel ill, and yet ultimately not benefit at all from the treatment.
But now, the many frustrated physicians, pharmacists, and parents who have to watch those children bear the extra burden of terrible side effects and lost time have real hope that such suffering will become part of medical history. Investigators at St. Jude Children’s Research Hospital are helping to create a new field of medical diagnosis and care. This field, called pharmacogenomics, is a cutting-edge technology for studying how populations of specific genes control an individual’s response to drug therapy. Such studies are identifying genetic variations in gender, race, and ethnic backgrounds that contribute to the success or failure of therapy.
One of the most prominent experts in this emerging field is Dr. William Evans, the scientific director and deputy director of St. Jude [editor's note: Dr. Evans is now the Director of St. Jude Children's Research Hospital]. A true pioneer in pharmacogenomics, he coauthored a major review of the field that was published in February 2003 in the prestigious New England Journal of Medicine.
This new approach to medicine gives physicians a genetic snapshot of each patient’s potential response to drug therapy – before treatment even begins. Using a technique called gene expression profiling, researchers study which of the genes that activate or break down drugs are active in a particular patient. These expression profiles are fingerprints that identify patients likely to benefit from treatment or suffer a toxic reaction. Thus, pharmacogenomics offers hope for lowering healthcare costs by speeding recovery, avoiding the complications of treatments, and shortening hospital stays.
Dr. Mary Relling is now leading a major NIH-funded program at St. Jude to identify the major pharmacogenetic determinants of treatment response in children with acute lymphoblastic leukemia (ALL), and she and her colleagues are world leaders in extending these studies to other catastrophic diseases in children.
In the clinic, St. Jude physicians now use pharmacogenomics to differentiate among the individual subtypes of ALL, each of which responds differently to chemotherapy. By using gene expression profiling to study cancerous white blood cells, St. Jude physicians can rapidly diagnose specific types of ALL, while eliminating the imprecise, labor-intensive process that previously required the combined expertise of several specialists (hematologist/oncologist, pathologist, cytogeneticist).
This new approach also has the potential to differentiate among those patients with ALL who can be treated with moderate doses of chemotherapy from those who should be treated aggressively. Thus, the strong medicine needed to treat cancers will be given in lower doses to those who can benefit fully from less aggressive treatment, while sparing them the worst side effects of treatment.
As data accumulate on the genetic basis for how the body metabolizes, transports, and responds to drug increases, it may become possible to select many drugs and their dosages based on the individual patient’s inherited ability to metabolize, eliminate, and respond to these medications. Thus, the field will impact not only the treatment of cancers, but also the treatment of asthma, depression, high blood pressure, and other medical conditions.
St. Jude is working hard to establish pharmacogenomics as a standard of care for specific diseases. This could encourage medical insurance coverage of this rapidly evolving approach to therapy; and that, in turn, would ensure that the benefits of this technology are available to all patients of all ages, and not restricted to only those patients who can afford it.