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Breast Cancer Drug Could Work for Some Lung Cancers

By Kate Ruder

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Breast Cancer
Lung Cancer
Personalized Medicine

Scientists have identified a small group of patients who have genetic mutations in their lung cancers that could make them sensitive to the drug Herceptin, which has been used with success in many patients with breast cancer. They found the mutations in five of 120 lung cancer patients they tested.

The mutations occur in the HER2 gene, and although the lung cancer mutations appear to be genetically different than the breast cancer mutations, the researchers are still hopeful that Herceptin could work. They caution that further tests are needed before the drug could be used for lung cancer.

Herceptin was designed in the laboratory to target the HER2 gene. It was first used in breast cancer, but when doctors tested Herceptin in lung cancer patients they didn’t have much luck. Yet, as with other highly selective new classes of tumor drugs, data suggest that it is important to use the right drug in the right patient, whose genetic profile is susceptible to the drug.

The new research was done by scientists at the Cancer Genome Project in the United Kingdom and appears in the journal Nature this week.

The findings are similar to the discovery earlier this year that a separate group of lung cancer patients with mutations in their tumors respond well to the targeted drugs Iressa and Tarceva.

This discovery was reported in two April 2004 studies by two groups of Harvard researchers, and the story has come to epitomize the potential of “personalized” medicine. The hope is that doctors could someday screen for mutations in tumors and then treat the tumor with drugs that would work best for each individual patient.

“We’d been looking for a year and a half at the HER2 gene when those studies came out,” says Andrew Futreal of Wellcome Trust Sanger Institute, United Kingdom, in reference to the Harvard studies.

“When we saw what they’d found we started pushing hard. It was the perfect model to think about our study. The same family of genes, very similar mutations, and potential group of targeted drugs,” he says.

In fact, the findings are exactly what researchers for the Cancer Genome Project were shooting for when they embarked on the project. One the primary goals of the project is to identify mutations in genes involved in cancer in order to find better targets for drugs.

“The fact that these mutations are present in a specific region of the HER2 gene was unknown and is of considerable interest,” says Daniel Haber of Massachusetts of Massachusetts General Hospital Cancer Center. Haber was not involved in the study.

“They have identified a ‘genetic subset’ of lung cancers that harbor these mutations. The next step will be to test with whether lung cancers that have these mutations are particularly responsive to drugs that inhibit HER2,” he says.

Futreal agrees that there is still much more work to be done before drugs such as Herceptin could be used for these patients, but he hopes that other researchers will see the paper and begin investigating the effects of drugs on these types of tumors.

“The study is really interesting,” says David Johnson of Vanderbilt-Ingram Cancer Center in Nashville, Tennessee. “I concur with the authors that we need repeat assessments of Herceptin in HER2 mutated lung cancer.”

So why hasn’t Herceptin shown any success in treating lung cancer patients, even in small numbers, so far? There could be several reasons, all of them speculative at this point.

“It remains to be seen whether antibody-based therapy like Herceptin does the trick,” says Futreal. “It’s really too provocative to say one way or another right now.”

Yet the studies show, at least for the moment, that there is potential even for well-known drugs such as Herceptin to work in a new group of patients. “There are new things under the sun even in well-trodden paths,” says Futreal.

Stephens, P. et al. Intragenic ERBB2 kinase mutations in tumours. Nature 431, 525-526 (September 30, 2004).

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