A team of researchers at Duke University has developed a new genetic test to help guide patient-specific chemotherapeutic treatments for cancer. The investigators used the gene chip made by Affymetrix to conduct their research. (See our earlier coverage: AmpliChip)
In experiments reported in the November 2006 issue of the journal Nature Medicine, the researchers applied the genomic tests to cells derived from tumors of cancer patients. They found that the tests were 80 percent accurate in predicting which drugs would be most effective in killing the tumor…
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 scientists successfully matched the right chemotherapy for the patient’s tumor type. The scientists were then able to validate their predictions against patients’ actual clinical 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 researchers anticipate that they will enroll approximately 120 patients with breast cancer in the study. Subsequent clinical trials will enroll hundreds of patients with lung and ovarian cancer, Potti said. [Anil Potti, M.D. is an assistant professor of medicine at Duke –ed.]
If proven effective, the tests could be applied to all cancers in which chemotherapy is given, not just breast, lung, and ovarian cancer, Potti said.
The researchers 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, scientists 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 scientists 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 scientists 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 researchers assessed the tests’ ability to predict how patients with breast and ovarian cancer and leukemia responded to various anticancer drugs. They found that the tests predicted the clinical response to chemotherapy with 80 percent accuracy.