New clues found to treat brain cancer

[Source: The Arizona Republic, Ken Alltucker] - A massive scan of tumor samples from a Phoenix lab has revealed new genetic clues about an aggressive form of brain cancer, which could open the door to new treatments and explain why some patients don't respond to a common chemotherapy drug.

The scientific findings, revealed Thursday, are the initial batch of results from the federal government's $100 million research initiative known as the Cancer Genome Atlas project.

Scientists from 18 groups, including the International Genomics Consortium in downtown Phoenix, identified three new wayward gene mutations for patients with glioblastoma - the type of brain cancer that U.S. Sen. Edward Kennedy, D-Mass., has.

Scientists say the brain-cancer study, based on an analysis of genetic samples from 206 patients, is important because it suggests new targets to fight the disease. All its findings will be available to university researchers or drug companies that want to take a crack at investigating new drugs.

Cancer researchers increasingly are seeking to uncover genetic links that lead to cancer and tumor growth with the idea that smarter, targeted drugs have the potential to slow or halt the disease.

IGC's tissue bank is the core of the federal government's three-year pilot project, which now will continue a study of lung and ovarian cancers.

"This has solidified Phoenix as a key player in molecular medicine," said Robert Penny, IGC chief operating officer. "We are the Grand Central Station for all tissue samples in this project."

Fast-growing tumor

The federal government expects about 21,000 new cases of brain cancer this year. Glioblastoma is the most common form of brain cancer found in adults and typically involves fast tumor growth. People diagnosed with this type of aggressive brain cancer typically die within 14 months of diagnosis.

The study's findings include identifying three new genetic mutations tied to glioblastoma and discovering clues that may help alter existing drug treatment.

"It does give us new pieces of information," said Dr. William Shapiro, chief of neuro-oncology at Barrow Neurological Institute. "This new information will have an effect on what we do today and very likely will have more of an effect on what we do in the future."

Barrow, located at St. Joseph's Hospital and Medical Center in Phoenix, treats 175 to 200 new patients each year with this type of brain cancer.

Shapiro said the life expectancy of patients with this disease was typically no more than four or five months in 1980. Now, many patients live two to three years or even longer with a standard treatment regimen that includes surgery to remove the tumor, followed by radiation and chemotherapy, he said.

Chemotherapy riddle

Still, doctors have been frustrated that some patients who take a common chemotherapy drug, known as Temodar (temozolomide), respond better than others. Doctors already know that the patients with an inactive MGMT gene seem to respond better to the chemotherapy drug.

The Cancer Genome Atlas team identified genetic mutations that may be linked to recurring tumors in such patients. That could give scientists more clues about how to use the drug Temodar in tandem with other drugs with greater success.

The other significant finding from the Cancer Genome Atlas team found three new genetic mutations that occur frequently with glioblastoma patients. The team also identified pathways, or clusters of genes, that are interrupted with great frequency in such patients.

Penny said, "We now believe that important information is out there that can lead to new targeted therapies and increased efficiency in treatment of these diseases."

Systematic approach

The National Cancer Institute and National Human Genome Research Institute launched the Cancer Genome Atlas project in 2006 in an attempt to bring a systematic genetic approach to cancer research. The goal: to yield fast-track therapies.

IGC was selected as the tissue bank from a field of 370 applicants that included many of the nation's top research universities. Scientists from the Harvard Medical School were part of the cancer genome team and were the lead authors on the glioblastoma study, which appeared in the Thursday edition of the journal Nature.

Now, the federal government must decide whether to expand the pilot project to an ambitious genetic study of more than 200 forms of cancer. Such a research project would last several years and cost $1.3 billion or more.

The National Institutes of Health Director Elias A. Zerhouni said that he is convinced that "it is time to move ahead and apply the power of large-scale, genomic research to many other types of cancer."

However, the Cancer Genome Atlas project has been controversial in some scientific circles, with critics saying that research money could be better spent on other methods of research.

A Johns Hopkins-led team conducted another cancer study, also released Thursday. The team examined genes in tumors taken from 24 pancreatic cancer patients and 22 patients with glioblastoma. The Johns Hopkins team concluded that the genetic riddle to cancer was even more complicated than previously thought, with no two tumors exactly the same.