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Drug response linked to genes in lymphoma patients
By Adam Marcus

Most patients with follicular lymphoma will take the drug rituximab at some point during their treatment, but only about 60 percent will get better. A new study suggests that doctors might soon be able to identify patients who will benefit from the drug by analyzing genes in their cancer cells.

Photomicrograph of follicular lymphoma superimposed on gene chip.

The researchers identified about 150 genes in lymph tumors that could help predict the drug response. The activity of these genes differed significantly between patients who responded to treatment and those who did not.

"If we could turn this into a prognostic test, we could say to some patients, 'Let's not mess around with rituximab, your odds of responding are low,'" says Sean P. Bohen, a cancer specialist at the Howard Hughes Medical Institute at Stanford University School of Medicine and leader of the study.

"We could then design clinical trials to test whether rituximab may benefit these patients in different dosing regimens or combined with other drugs," Bohen adds.

The second most common form of lymphoma, follicular lymphoma typically progresses slowly; the average patient survives for at least a decade after their diagnosis.

Because follicular lymphoma develops so gradually, doctors often take a 'watchful waiting' approach before starting treatment with any anticancer drugs. The lymphoma usually responds to chemotherapy at first but eventually the patient suffers a relapse. These patients go on rituximab, which is sold as Rituxan.

The researchers identified the 150 genes using 'gene chips,' which are glass slides or microchips that contain DNA from thousands of genes. They show whether a set of genes is active in a cell.

One of the gene chips in the study was a modified version of the 'Lymphochip.' This specialized gene chip includes roughly 10,000 genes associated with cancer and immune cells. The modified version has nearly 18,000 genes.

The study involved 24 people, and the work will need to be confirmed in a larger group before doctors consider trying to apply the results in the clinic. "I think it's a very provocative first-stage study that requires confirmation on a separate and hopefully larger population," Bohen says.

Wing C. Chan, a pathologist at the University of Nebraska Medical Center, in Omaha, calls the latest work "a nice preliminary study that has to be confirmed by additional cases." Chan, who has helped test the Lymphochip in patients, says the device currently has too many genes to be useful clinically. The ideal chip, in his view, might contain fewer than two hundred genes.

"The large chips are useful for research, but we will eventually have to eliminate genes," Chen says.

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Bohen, S. et al. Variation in gene expression patterns in follicular lymphoma and the response to rituximab. Proc Natl Acad Sci USA 100, 1926-1930 (February 18, 2003).

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