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Cancer researchers are learning to read genes like a crystal ball to predict how patients will respond to cancer therapy, who will suffer the worst side effects and what treatments may be best for a particular patient. Foreseeing the outcome of treatment, and knowing with certainty which drugs are best for individual patients, have long been the goals of cancer researchers.
For at least 40 years, oncologists have puzzled over why some patients respond so well to chemotherapy while others obtain modest benefits or none at all. The discovery decades ago that linked a chromosome abnormality to one form of leukemia paved the way for the development of the drug Gleevec by Druker and the ability to identify the patients most likely to benefit. More recently, with the wealth of knowledge from the Human Genome Project, researchers have been able to develop even more specific tools to create genetic profiles of tumors and match those profiles with the right drugs. The tools also help determine which patients are most likely to experience the worst side effects of specific types of chemotherapy and guide them to other treatments.
Researchers from the University of Chicago studied alterations of the UGT1A1 gene, associated with an increased chance of chemotherapy side effects. Mark Ratain and his team studied 61 colon cancer patients receiving irinotecan and learned that patients with alterations of the gene labeled as 7/7 were most likely to suffer severe losses of white blood cells. Patients with the 6/7 alteration type had intermediate side effects, and patients with the 6/6 type had none.
Scientists at the Massachusetts General Hospital examined genes that normally have the ability to repair damage to DNA in cells called XPD and XRCC1. The number of variations in these genes indicate how long a patient is likely to survive. Sarada Gurubhagavatula and her team studied variations of these genes in 103 patients diagnosed with advanced non-small-cell lung cancer. Patients with a total of three variations in the genes survived a median of 6. 8 months; those with two variations survived 11 months; patients with one variation survived 16.6 months; and those with no variations survived 20.4 months. Gurubhagavatula says the variations could be identified and those with the worst predicted outcomes put on chemotherapy regimens that offer better odds of survival.
Scientists at Cedar-Sinai Medical Center and Genomic Health Inc. have developed a way to test lung tumors for genetic profiles associated with responses to the new lung cancer drug Iressa. The drug has been shown to shrink tumors in 10% to 12% of patients with advanced lung cancer. David Agus at Cedar-Sinai found a pattern of 185 genes that are turned off and on in a manner that correlates with response to Iressa or to a lack of response. When used commercially, the test will target patients most likely to benefit and will allow patients to make other choices if the negative profile is found.