the future is now: they are already starting using genetic profiling of tumors to

[Lani]

individualize which chemotherapy (and immunotherapy) agents to give to patients:


Genomic Tests Might Soon Guide Choice of Chemotherapy

October 30, 2006 — Researchers have uncovered early evidence that might help predict response to commonly used cytotoxic agents. They suggest that therapy will soon be tailored to individual patients and the traits of their particular tumor. "Over 400,000 patients in the United States are treated with chemotherapy each year, without a firm basis for which drug they receive," senior author Joseph Nevins, PhD, a professor of genetics at the Duke Institute for Genome Sciences and Policy in Durham, North Carolina, said in a news release. “We believe these genomic tests have the potential to revolutionize cancer care by identifying the right drug for each individual patient."

Reporting in the November issue of the journal Nature Medicine, published early online, the researchers used in vitro drug-sensitivity data coupled with microarray gene-expression data to develop gene-expression signatures and predict sensitivity to individual chemotherapeutic drugs. Under the direction of lead author Anil Potti, MD, also from Duke, the group validated each signature with response data from an independent set of cell-line studies.

The research team points out in their paper that the practice of oncology continually faces the challenge of matching the right therapeutic regimen with the right individual and balancing relative benefit with risk to achieve the most favorable outcome. "This challenge is often daunting, with marginal success rates in many advanced disease contexts — probably reflecting the enormous complexity of the disease process coupled with an inability to properly guide the use of available therapeutics."

Improving Efficacy Without Altering Repertoire of Drugs

The researchers point to recent studies that have demonstrated the value in using biomarkers to select individuals for various targeted therapeutics, including tamoxifen, trastuzumab, and imatinib mesylate. They note that the importance of selecting individuals likely to respond to a given therapeutic agent is perhaps best illustrated by the example of trastuzumab. "In the absence of selection, the overall response rate in people with breast cancer is approximately 10%. In contrast, for those selected on the basis of HER2 amplification, the overall response rate rises to 35 to 50%," they write.

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

In the current study, funded by the National Institutes of Health, the researchers found that the tests were 80% accurate in predicting which drugs would be most effective. "We show that these signatures can predict clinical or pathologic response to the corresponding drugs, including combinations of drugs," they explain. "We further use the ability to predict deregulated oncogenic signaling pathways in tumors to develop a strategy that identifies opportunities for combining chemotherapeutic drugs with targeted therapeutic drugs in a way that best matches the characteristics of the individual."

The Duke team plans to begin a clinical trial of the genomic tests in breast cancer patients next year. The 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 a trial-and-error manner. The group plans to enroll 120 patients in the study. Dr. Potti reported in a news release that subsequent clinical trials will enroll hundreds of patients with lung and ovarian cancer.

Nat Med. Published online October 22, 2006.