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Medicineworld.org: Choosing Chemotherapy Using Genomics

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Choosing Chemotherapy Using Genomics

Choosing Chemotherapy Using Genomics
Researchers at Duke University's Institute for Genome Sciences & Policy have developed a panel of genomic tests that analyzes the unique molecular traits of a malignant tumor and determines which chemotherapy will most aggressively attack that patient's cancer.

In experiments published in the November 2006 issue of the journal Nature Medicine, the scientists applied the genomic tests to cells derived from tumors of cancer patients. They observed that the tests were 80 percent accurate in predicting which drugs would be most effective in killing the tumor.

The Duke team plans to begin a clinical trial of the genomic tests in patients with breast cancer next year.

The new tests have the potential to save lives and reduce patients' exposure to the toxic side effects of chemotherapy, said Anil Potti, M.D., the study's lead investigator and an assistant professor of medicine in the Duke Institute for Genome Sciences & Policy. The tests are designed to help doctors select and initiate therapy with the best drug for a patient's tumor instead of trying various drugs in succession until the right one is found, Potti said.

"Over 400,000 patients in the United States are treated with chemotherapy each year, without a firm basis for which drug they receive," said Joseph Nevins, Ph.D., the study's senior investigator and a professor of genetics at the Duke Institute for Genome Sciences & Policy. "We believe these genomic tests have the potential to revolutionize cancer care by identifying the right drug for each individual patient".

The tests work by scanning thousands of genes from a patient's tumor to produce a "genomic" profile of the tumor's molecular makeup. Using the genomic tests in cancer cells in the laboratory, the researchers successfully matched the right chemotherapy for the patient's tumor type. The researchers were then able to validate their predictions against patients' actual clinical outcomes.

Doctors currently must use a trial-and-error approach to chemotherapy, trying various established drugs to see which has an effect. As a result, patients often undergo multiple toxic therapies in a process that places patients' lives at risk as their conditions worsen with each therapy.

"Chemotherapy will likely continue to be the backbone of a number of anticancer therapy strategies," said Potti. "With the new test, we believe that physicians will be able to personalize chemotherapy in a way that should improve outcomes".

The first clinical trial will compare how well patients respond to chemotherapy when it is guided by the new genomic predictors versus when it is selected by physicians in the usual trial-and-error manner. The scientists anticipate that they will enroll approximately 120 breast cancer patients in the study. Subsequent clinical trials will enroll hundreds of patients with lung and ovary cancer, Potti said.

If proven effective, the tests could be applied to all cancers in which chemotherapy is given, not just breast, lung, and ovary cancer, Potti said.

The scientists developed the new tests through a process that included analyzing the activity of thousands of genes in cells taken from the tumors of cancer patients.

In using the test, researchers extract the genetic molecule "messenger RNA" from a cancer patient's tumor cells. Messenger RNA translates a gene's DNA code into proteins that run the cell's activities. Hence, it is a barometer of a gene's activity level inside the cell.

The researchers then label the messenger RNA with fluorescent tags and place the labeled molecules on a tiny glass slide, called a gene chip, which binds to segments of DNA representing the tens of thousands of genes in the genome.

When scanned with special light, the fluorescent RNA emits a telltale luminescence that demonstrates how much RNA is present on the chip, and this reading indicates which genes are most active in a given tumor. The researchers use this signature of gene expression in the cancer cells to predict which chemotherapeutic agent will be most powerful in treating the specific tumor.

In the current study, funded by the National Institutes of Health, the scientists assessed the tests' ability to predict how patients with breast and ovary cancer and leukemia responded to various anticancer drugs. They observed that the tests predicted the clinical response to chemotherapy with 80 percent accuracy.

"Importantly, we believe this research can improve the efficiency of chemotherapy without changing the drugs currently used in standard practice," Nevins said. "Rather, the tests simply provide an approach to better selection, within a repertoire of available drugs".


Posted by: Janet    Source




Did you know?
Researchers at Duke University's Institute for Genome Sciences and Policy have developed a panel of genomic tests that analyzes the unique molecular traits of a malignant tumor and determines which chemotherapy will most aggressively attack that patient's cancer. In experiments published in the November 2006 issue of the journal Nature Medicine, the scientists applied the genomic tests to cells derived from tumors of cancer patients. They observed that the tests were 80 percent accurate in predicting which drugs would be most effective in killing the tumor.

Medicineworld.org: Choosing Chemotherapy Using Genomics

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