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Study shows developing a gene therapy for cancer will be harder than scientists thought

Scientists working to customize cancer treatment based on each person's genes are finding new evidence of just how tough this task will be.

In a single tumor, there are big differences as to which genes are active or mutated. Nor are the genetics of a single tumor and where it has spread consistent.

This means that the single biopsies that doctors rely on to choose drugs are probably not giving a true view of the cancer's biology.

"We're finding that the deeper you go, the more you find," said one study leader, Dr. Charles Swanton of the Cancer Research UK London Research Institute. "It's like going from a black-and-white television with four pixels to a color television with thousands of pixels."

The study, reported earlier this month in the New England Journal of Medicine, is a reality check for "overoptimism" in conquering cancer with new gene-targeting drugs, wrote deputy editor Dr. Dan Longo in an editorial.

About 15 of these medicines are on the market now and hundreds more are in testing, but they have had only limited success. The new study may help explain why.

"We anticipated this,'' said Dr. Robert Gatenby, chairman of the department of radiology at Moffitt Cancer Center in Tampa. "The study confirms what researchers in the field have long known or suspected to be true. The idea that we could take a little snip of a tumor and understand a whole disease was always overly optimistic."

Gatenby also is co-director of the integrated mathematical oncology program, a key part of Moffitt's customized treatment called Total Cancer Care.

He said a key is anticipating how tumors behave and evolve. "We have evolutionary biologists and mathematicians working with a super-computer at USF assessing the variations in tumors and thinking of them in multiple different habitats and stages of growth," Gatenby said.

"We use those changes, those dynamics in our favor … By using sophisticated approaches we can reduce the tumor and force it in directions that give us new therapies."

For the new study, scientists used gene sequencing to a degree that has not been done before to study primary tumors and places where they spread in four patients with advanced kidney cancer. Two-thirds of gene mutations they detected were not present in all areas of the same tumor. They also saw different mutations in the same gene from one part of a tumor to another.

That means a single biopsy would reveal only a minority of mutations. Still, it's not clear whether doing more biopsies would improve accuracy, or how often they should be done.

Independent experts said the results should apply to other cancers such as breast, lung and colon.

"This is an important paper," said Dr. Gordon Mills, co-director of the Institute for Personalized Cancer Therapy at the University of Texas MD Anderson Cancer Center.

Doctors there have been offering genetic testing to patients for several years and have a database of results on about 4,000 tumor samples. So far, about 40 percent of breast cancers have discrepancies between which genes are active in the main tumor and which ones are active where the cancer has spread, Mills said.

At Moffitt, the Total Cancer Care program has enrolled more than 50,000 patients since 2005 whose tissue samples are being stored in hopes of developing new therapies.

Gatenby used this analogy to describe how scientists are tackling ever-changing cancers: "Watch pool players. They not only get a specific ball in a specific pocket, but they anticipate their next shot and put the white ball where it needs to be, so the next shot is set up for them. That's how cancer care will go. We embrace the evolutionary process and use it to our advantage."

Information from the Associated Press and Times staff writer Irene Maher was used.

Study shows developing a gene therapy for cancer will be harder than scientists thought 03/14/12 [Last modified: Wednesday, March 14, 2012 10:31pm]
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