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Genetic profiling used to tailor cancer therapy

April 21, 2009 By Kendall Powell This article courtesy of Nature News.

Tumour screening leads to more effective treatment for some patients.

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About a quarter of patients with drug-resistant tumours lived for longer after genetic screening of their tumours allowed them to be switched to better targeted treatments.

Many researchers believe that this type of personalized medicine, in which treatments are designed around an individual's genetic profile, may be the future of cancer treatment.

The results of the pilot study were presented on 20 April at the American Association for Cancer Research (AACR) annual meeting in Denver, Colorado.

"This is a very strong step in the right direction and it's very encouraging," said Ronald DePinho of the Dana-Farber Cancer Institute in Boston, Massachusetts, who was not involved in the study. "These are obviously preliminary results but they nevertheless provide a visibility of how to profile patients for the huge number of drugs available."

Spearheaded by Daniel Von Hoff, physician-in-chief of the Translational Genomics Research Institute in Phoenix, Arizona, the study was conducted at 9 cancer centres around the United States and included 66 patients. The patients all had cancers that had spread, or metastasized, from the primary tumour site and were all on drug regimens that had stopped working.

Von Hoff's team wanted to know whether molecular profiling of these patients' cancers could identify different drugs on which the patients might fare better. The researchers screened each patient's cancer tissue against a panel of 55 genes that are implicated in cancer and can also be targeted by commercially available drugs.

Using antibody screens and DNA microarrays, the group identified the genes with the highest levels of expression — and presumably activation — in the cancer tissue. On the basis of the top one or two gene 'hits', the researchers recommended starting a patient on the one or two drugs that target those genes.

Tailored treatment

At the start, Von Hoff set a simple goal: at least 15% of the patients in the study needed to show improvement in survival for this approach to be worthwhile. In the end, 18 of the 66 patients — that is, 27% — fared better on the new drugs based on molecular profiling than they had on their previous drug therapy. This was measured by comparing the time period during their previous drug regimen in which their disease did not advance with the period of time without disease advancement on the new drug treatment.

The 18 patients who improved after molecular profiling had an average overall survival of 9.7 months, compared with an average of 5 months for the whole group.

This type of molecular profiling is not routine for most patients with cancer, although the Massachusetts General Hospital in Boston and Memorial Sloane-Kettering Cancer Center in New York have begun similar screening for some patients (see 'Personalized cancer therapy gets closer'). But it's not terribly complicated or costly, says Von Hoff.

"There would be no reason that you cannot do this tomorrow" for patients with metastatic cancer who aren't responding to drugs, Von Hoff says. He makes it clear that the study should be repeated in a randomized controlled trial, in which patients are split into a molecular profiling group and a control group that does not receive profiling, to ensure that the improvements are due to the profiling. "It's not ready for prime time in patients with no prior treatment history."

Personalized medicine is moving forwards because technologies are now available that allow genetic screening or sequencing of tumours to be done "carefully and in a short time", says Michael Caligiuri, director of the Comprehensive Cancer Center at Ohio State University in Columbus and programme chairperson of the AACR meeting. "It's getting easier and more cost-effective to do these kinds of studies."

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