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Outwitting 'smart' cancers with Genomics Tumor Board
Helen Adams | adamshel@musc.edu | April 26, 2016



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Clues to fighting cancer are being revealed through genomic analysis, which looks at the DNA of cancer cells for mutations to target. 

If doctors could give tumors IQ tests, unfortunately, some would qualify as gifted. They’re what doctors call “smart” cancers: They keep mutating and outwitting efforts to kill them.

But a new Genomics Tumor Board at the Medical University of South Carolina may help even the odds. 

Dr. John WrangleJulia Lynn 
Dr. John Wrangle says he welcomes the insight the Genomics Tumor Board offers in cancer cases where treatment options are tricky. 

Oncologist John Wrangle, M.D., said it may have already helped him outsmart one patient’s non-small cell lung cancer. “I have a patient whose tumor harbored a typical mutation that portends sensitivity to a pill.” In other words, at first, it looked like a traditional treatment would work.

Not so fast, he soon realized. “Broad mutation testing revealed a second, extremely uncommon mutation.” So Wrangle worked with the Genomics Tumor Board, a panel of medical doctors and researchers that meets monthly at Hollings Cancer Center, to find a better option.

“Because of my concern that this would yield primary resistance to therapy, we embarked on a clinical trial of an alternate first-line therapy that may overcome inherent resistance to treatment.” There was new hope.

That kind of nuanced decision making is what the Genomics Tumor Board is all about. It focuses on cancer cases where treatment choices are tricky, using the collective wisdom of board members to make the most sophisticated recommendations possible. They look at about a dozen carefully selected cases each month with an emphasis on lung cancer, colorectal cancer, melanoma and metastatic cases.

Dr. Stephen Ethier 
Dr. Stephen Ethier, who directs MUSC's Center for Genomic Medicine, says it's time to stop guessing. "The answer is in the genome." 

For the director of the Center for Genomic Medicine, Stephen Ethier, Ph.D., the board’s creation is the result of more than two years’ worth of effort as he pushed for it to become a reality. He put the board’s purpose this way: “We have to stop guessing. The answer is in the genome. Ultimately, every patient is going to be treatable from what we learn from their genomic analysis.”

Genomic analysis looks at the DNA of cancer cells for mutations to target. Steven Carroll, M.D., a key player on the Genomics Tumor Board and chairman of the Department of Pathology and Laboratory Medicine, said it’s a new way of thinking about cancer. 

“We’ve done pathology the same way for a few hundred years. It’s pretty much been a matter of – you take a look at the tissue through the microscope and say, ‘Yes, we know what this tumor is. And based on a cohort of patients, we know how it’s going to behave.’”

But it’s never been that simple, he said. Sometimes cancer treatments work, but other times, they fail miserably. So scientists started taking a closer look at the makeup of cancer. They began with glioblastomas, brain tumors that are tough to treat, and found something remarkable.

“The glioblastoma tumors all looked the same under a microscope,” Carroll said. “But when we went beyond that to the molecular level, there are actually four different kinds of glioblastomas. They have different mutations, and with different mutations, they’re going to respond to different drugs.”

Dr. Steven CarrollSarah Pack 
Dr. Steven Carroll speaks to a packed room at a recent Genomics Tumor Board meeting. 

It was a breakthrough with big implications, Carroll said. “You can now get a therapy that really goes after what’s wrong with your cancer.”

Genomic sequencing also opens the door to basket trials, one of the newer ways to test cancer treatments. They emphasize gene mutations instead of cancer types.

Most hospitals don’t offer the type of sequencing available at MUSC. Carroll wants to get the word out. “We want to be able to offer patients hope they couldn’t get out of their community hospitals.”

But this is where a reality check comes in. There are not drugs for every mutation. 

Genomic sequencing is also extremely complex, Carroll said. “This is really still the Wild West in terms of analytics. These are huge data sets.” 

And in many cases, genomic sequencing simply isn’t needed. These are the cancers that would fail the theoretical IQ test. “Dumb cancers have pretty straightforward abnormalities that you can target,” Carroll said. They respond to chemotherapy or radiation.

The smart cancers are “complex beasts,” Carroll said. “Everyone thinks there’s just one clone of cells that expands and you get a cancer. But that’s actually not true. They keep mutating.”

Dr. Cynthia Schandl 
Dr. Cynthia Schandl 

Fortunately, the science of fighting cancer is mutating too, picking up important IQ points as researchers and doctors learn more about how cancer works and how to beat it. The new Genomics Tumor Board, led by Cynthia Schandl, M.D., Ph.D, and the 3-year-old Center for Genomic Medicine, which serves as a hub for research and treatment related to genetics and genomics at MUSC, are important parts of that, Ethier said.

He knows from personal experience how important this work is. “The type of breast cancer my mother died from is the exact type that I work on in my lab,” Ethier said.

“We’re making progress in this disease – cancer. We’re getting better. This is the next frontier in that. This is how we’re going to continue to do better with more patients and effect more cures. We need to cure a lot more.” 

Wrangle agreed. “Without a sophisticated approach to analyzing complex data, pairing patients with next generation therapies is not possible.”

 

 

 

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