Study May Reveal Custom-Tailored Cancer Treatments

DURHAM, N.C. (November 2005) — Researchers at Duke University Medical Center have taken another step toward curing cancer.

Joseph Nevins, Barbara Levine Professor of Breast Cancer Genomics, has headed a new study that may eventually allow doctors to tailor drug prescriptions for individual patients. The study was published in the November issue of Nature, one of the world’s most respected science journals.

“It’s the future of cancer therapy,” said Dr. Michael Colvin, director emeritus of the Duke Comprehensive Cancer Center.

Nevins and his colleagues used DNA microarrays, which can identify the specific activities of gene expression in a cell, to classify tumors according to which drugs would affect them.

In cancer cells, normal pathways of gene expression are disrupted, Nevins explained. As a consequence, several “checkpoints” that regulate cell growth fail to function properly, allowing for the uncontrolled growth that forms a tumor.

“We have a series of profiles that serve as signatures for those pathways,” Nevins said. The specific changes in these pathways, however, can vary from person to person.

Using the methods of Nevins’ study, doctors would be able to choose the drugs that are most likely to combat an individual patient’s cancer.

While many drugs exist that target specific aspects of cancer, deciding which ones to use can be a daunting task. “The fact of the matter is there are upwards of maybe 50 drugs that are developed that target specific components of cancer cells,” Nevins said.

But often, tumors do not respond to a particular treatment, noted Andrea Bild, research associate at the Center for Genome Technology and lead author of the paper.

“The advantage of this treatment is that we could target something we predict would be deregulated, whereas other treatments take a more global approach,” she said.

A patient-specific approach could help produce a higher survival rate. “There has been a major effort in the last several years to understand the pathways that drive cancer,” Colvin said.

Nevins explained that the complexities involving these different pathways pose a major difficulty in treating cancer. “I think most people would agree that a cure… is not likely to happen with one drug,” he said.

Instead, substantially effective treatments will involve using a combination of drugs, Nevins said.

The next step in exploring the method will be clinical trials in which patients receive their own tailored treatments.

Since drugs that are already in use are known to target certain pathways, researchers could profile a patient’s specific case of cancer, prescribe a combination of drugs based on that profile and look for an increase in his response rate. “I’m certainly confident in the results that we have right now, especially in patient tumor samples,” Nevins said.

He added, however, that his team will not know the efficacy of their approach toward humans until the completion of the clinical trials. Testing could begin in the next six months and would initially make Duke the only place in the world to offer such a treatment, Nevins said.

If successful, the trials would be expanded to other institutions.

Nevins also noted that some clinical trials and subsequent developments will require more funding, which could lead to an increase in grants for DUMC.

At the moment, many researchers are hopeful that the new method will benefit patients.

“It’s nice when something you’re working on has translational applications,” Bild explained. “We’re all very excited.”

Contact: Christina Patsiokas