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Patients with mutation benefit most from lung cancer drug
Source: (cancerfacts.com)
Thursday, April 29, 2004
BOSTON – April 29, 2004 – In a study that stands to benefit thousands of patients with non-small cell lung cancer around the world, U.S. and Japanese researchers have found that patients with a particular protein marker gain substantial benefit from treatment with a new generation drug, called gefitinib.
Researchers at Dana-Farber Cancer Institute in Boston and Nagoya City University Medical School in Japan found that tumors with an abnormal version of a protein called epidermal growth factor receptor (EGFR) shrink dramatically when exposed to the drug gefitinib, sold as Iressa™.
The drug is the second anti-cancer drug developed that specifically targets a genetic mutation commonly found in cancer cells, according to the study's co-senior author Dr. William Sellers of the Dana-Farber Cancer Center.
By scanning the DNA of cancer cells, researchers hunt for mutated genes that instruct cells to produce abnormal versions of growth proteins called tyrosine kinases. The hope is that drugs known to block such proteins can halt cancer growth while leaving normal cells intact. The first successful drug developed this way is Gleevec®, commonly referred to as the "leukemia pill" approved by the FDA nearly two years ago.
"Imatinib (Gleevec™) is probably the best-known example of a drug that works by targeting a specific, mutated tyrosine kinase," Sellers said in a prepared statement. "So far, though, this approach has been most notable in cancers that are relatively rare. Our study shows that it can be effective for a common form of cancer as well."
Non-small cell lung cancer accounts for about 85 percent of all cases of lung cancer, the number one cancer killer of both men and women in the United States.
The study will be published this week in the online version of the journal Science. Related research from Massachusetts General Hospital Cancer Center, a member of the Dana-Farber/Harvard Cancer Center, will be concurrently released online by the New England Journal of Medicine today.
"Until now, there has not been a great deal that medicine could do for most patients with non-small cell lung cancer," says Dr. Matthew Meyerson, also of Dana Farber and faculty member of the Broad Institute and Harvard Medical School. "This study is the first indication that a therapy targeted for a specific group of patients can have an impact on this disease. It demonstrates how the growing understanding of human biology and the Human Genome Project are converging to produce an immediate effect on cancer care."
In the study, Dana-Farber and Broad Institute investigators led by Meyerson and Sellers scanned non-small cell lung tumors from 58 Japanese and 61 American patients for gene mutations. While just one of the American patients had a mutation in the EGFR gene, 15 of the Japanese patients did. The investigators knew from previous research that Iressa, an EGFR kinase blocker that has had only sporadic success against NSCLC, shrinks such tumors more frequently in Japanese patients than in Americans.
Meanwhile, study co-authors Drs. Bruce Johnson of Dana Farber and Pasi Janne of Brigham and Women's Hospital found that tumor tissue from a woman with cancer that had spread to the lining around her lungs – a condition called adenocarcinoma – was very responsive to gefitinib when tested in a laboratory dish. When the adenocarcinoma's DNA was analyzed, it was found to have the same EGFR gene mutation that Meyerson and Sellers' group had found.
"We were struck that certain groups of non-small-cell lung cancer patients appear to be more likely to have EGFR mutations than others," Johnson remarks. "Mutations were more frequent in women, in Japanese patients, and in patients with adenocarcinoma. These are the exact same groups that are most likely to experience tumor shrinkage when treated with gefitinib. Because Iressa is an EGFR inhibitor, we reasoned that patients with EGFR mutations might be especially responsive to treatment with Iressa."
To test that idea, investigators analyzed tumor samples from five patients who had been successfully treated with Iressa and four patients whose tumors did not respond. All of the responders were found to have EGFR mutations, while none of the four whose lung cancers did not respond had such mutations.
"Our results suggest that screening patients for EGFR mutations can help predict whether they will be responsive to treatment with Iressa," says Johnson, who is also a faculty member at Brigham and Women's and Harvard Medical School. "They also point to the fact that certain ethnic populations may benefit from Iressa therapy to a greater degree than others."
The Dana-Farber team's next step will be to conduct clinical trials to determine if combining Iressa with other targeted treatments can benefit patients not helped by Iressa alone. They hope to undertake these studies with colleagues at Massachusetts General Hospital who are also engaged in kinase research.
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