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| Archive : Summer
2006 |
WHEN A PATIENT'S GENES EXPRESS THEMSELVES, THEY MIGHT:
Suggest that a certain treatment is almost sure to work // Signal that heart transplant rejection is imminent // Advise against chemotherapy // Issue other messages we don’t yet understand.
Medicine Gets Personal [page 2]
 By Anita Slomksi
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By dovetailing the HapMap with new technology that allows scientists to put microscopic samples of DNA on a chip and scan thousands of genes at a time, as well as computer programs that can analyze vast amounts of genetic data, Tanzi can test for a gene variant at average increments of 5,000 DNA base pairs on the 3-billion-base-pair genome—compared with having to screen genes in groups of 50 million base-pair regions before.
Amid this ongoing hunt for individual genes, many practical applications of personalized diagnosis and treatment are flowing from genomics, the study of gene expression. Because the amount of RNA a gene expresses may vary in different tissues and tumors, it can be a very sensitive measure for, among other uses, distinguishing one tumor from another. Genomics tests that gauge those variations have the potential to help physicians determine what treatment is needed and when and how effective it’s likely to be.
Many of these tests, some making their way into clinical practice, involve cancer. “Genomic differences can vary widely among individuals, resulting in variable responses to therapy, even for patients whose cancers seem identical under a microscope,” says Randy Scott, president and CEO of Genomic Health, which provides a test that attempts to predict whether estrogen-sensitive breast cancer is likely to recur and whether a woman needs chemotherapy as well as the hormonal treatment tamoxifen.
Genomic Health’s Oncotype DX test measures the amount of RNA expressed by 16 genes in early-stage breast cancer tumors sensitive to estrogen. “Some of the genes are good and some are bad,” says Scott. “The relative amounts that each tumor expresses show how aggressive the tumor is.” A high score, earned by about a fourth of tumors, indicates that the cancer is too aggressive to be tamed by tamoxifen alone and will require chemotherapy as well. Conversely, the test can also identify women who might safely skip chemotherapy, sparing them the trauma and expense of needless treatment.
Other tests can help doctors time a drug for maximum effect—a particular benefit when prescribing potent immunosuppressants and steroids for transplant patients. Working from a blood sample, the genomics test AlloMap measures the RNA expressed by 20 genes in leukocytes (white blood cells) for signs that a heart transplant patient’s immune system is about to launch an attack against the heart. Before this test was developed, the only way to monitor a patient for signs of organ rejection was to snake a catheter into the new heart and snip off several pieces of heart muscle for biopsy—a risky procedure typically repeated 25 times in the first four years after transplant.
In some 30 transplant centers, cardiologists use AlloMap in addition to biopsy to alert them when rejection is imminent. If AlloMap indicates that the patient is not rejecting the heart, physicians may decide to forgo biopsies and continue weaning the patient off antirejection drugs, says Pierre Cassigneul, president and CEO of XDx Inc., the maker of AlloMap. “The test helps clinicians identify when the immune system is in check. Ultimately, clinicians want to decrease long-term side effects by lowering the immunosuppression without increasing the risk of rejection. But they also want to intervene before rejection—and irreversible damage to the heart—occurs.”
Still other genomics tests could benefit psychiatric patients. Wolfgang Sadee, professor of medicine and pharmacology at Ohio State University, expects that within five years he’ll identify gene variants that alter drug receptor activity and the metabolism of antipsychotic drugs. Finding those 10 to 20 genes should enable him to develop a test that will predict who will respond to a particular treatment, avoiding a trial-and-error approach to gauge whether a particular drug is working. “When you prescribe an ineffective drug, the patient suffers,” Sadee says. “Each episode of psychosis causes lasting damage.” |
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Photo by Lee Williams; Photo of Hand: Don Farrall/Getty
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