WASHINGTON, DC—Over the next two years, the National Cancer Institute (NCI) will grant over $1.3 billion to researchers across the nation to help spur initiatives that are expected to progress understanding of cancer into the 21st century. According to NCI officials, an unprecedented convergence of advances in molecular biology and other advanced technologies is on the verge of transforming researchers’ understanding of the mechanisms behind the disease.

The Cancer Atlas

“Cancer is a disease of changes in our genes,” NCI Deputy Director Anna Barker, PhD, told legislators at a House Energy and Commerce Health Subcommittee hearing last month. “We’re systematically identifying these genomic changes in cancer, which is allowing us to finally identify the molecular basis or subclasses of cancer and develop targeted interventions. That’s quite a step.”

The mapping of the human genome has paved the way for a revolution in how cancer is treated. With the cost of sequencing genomes falling at an ever-increasing rate, the possibility of understanding cancer at the genetic level and sculpting personalized treatments accordingly is ever-increasing as well.

In 2005, NCI and the National Human Genome Research Initiative teamed up to begin work on The Cancer Genome Atlas, the largest and most comprehensive analysis of the molecular basis of cancer ever undertaken. The pilot project that kicked off the TCGA was an analysis of geo-blastoma (GBM) —which is the most prevalent human brain tumor in adults, ovarian cancer, and lung cancers.

“In 2008, the first mega results of the TCGA pilot program produced a map of the three key pathways that are disrupted in GBM and defined the four specific electric sub-types of this cancer, paving the way for identifying the right patient for the right drug,” Barker explained. “The availability of the highest quality multi-dimensional data set or a statistical set of high-quality samples is bringing new investigators and teams forward to study GBM in large numbers.”

This convergence of researchers was one of the original goals of TCGA—bringing as many minds as possible to the table to study a particular type of cancer. And the project is about to do the same thing for high-grade ovarian cancer, which is suspected for most ovarian cancer deaths and is a major contributor to the overall 5-year survival rate of only 31%. While the data from TCGA’s analysis of ovarian cancer is still being finalized for publication, Barker gave legislators a sneak-peak.

“Ovarian cancer is a disease of copy number change, which is means [it’s caused by] a disruptive genome. This instability is likely driven by nearly wholesale changes in only three genes. These are three distinct molecular sub types of ovarian cancer confirmed at multiple levels of the genome. The distinct pathway is disrupted in ovarian cancer and their signature predicts survival duration. That’s quite a finding.”

Researchers found that the tumor is driven by defects in genes responsible for repairing damaged DNA, which creates new targets for drug development. “The data is going to open up a whole range of new windows of exploration for diagnosis and treatment of ovarian cancer that I predict will change the future for ovarian cancer patients, hopefully
on an accelerated schedule,” Barker declared.

Using Recovery Act funding, NCI has opened up the scope of TCGA, expanding it to explore 20 additional cancers over the next five years.

The Hurdle of Sample Quality

Choosing which cancers NCI focuses its resources on is a very delicate balancing act, Barker told legislators. There are, at last count, over 400 cancer-related survivor groups, each advocating additional research on one particular type of cancer, she explained. “So what we try to do is to look at what’s really promising in terms of what’s going to enable cancer research that will actually be translatable to patients, and backing into that, what’s going to inform the biological space that will allow that to happen.”

One of the biggest obstacles is something that cannot be easily put aside: the availability of samples for study. When TCGA began its work looking at GBM, researchers looked everywhere in the United States for biosamples, but eventually needed to broaden their search internationally. And only about 30% of samples collected were of the right quality to be useful for the Atlas. Since then, NCI has found that the 30% ratio can be found in all cancer samples in the country.

“People collected these samples over many years. They weren’t thinking a lot, when they collected the samples, about the advanced technologies we’d be using today,” Barker explained. “So, in terms of selecting cancers for the Atlas, the first priority is: Are the samples there? Are they available?”

TCGA has since created a set of best practices for collecting biosamples that it hopes researchers will follow. “As we move forward, we think that we will also be able to prospectively collect samples and that will be driven mostly by which tumors are prevalent and which ones we can actually lay our hands [on] in the most rapid fashion,” Barker said. “But we can collect tumors prospectively now and actually make sure that they meet our very stringent criteria.”

Digitizing Cancer

The best word to describe what is necessary in the juggling of research priorities is “balance,” Barker explained. There needs to be both a balance in what cancers are focused on and in what type of research is being funded.

“If we can actually balance the amount of individual investigator-initiated research with some of these larger programs, I think we will proceed faster,” Barker said. “I think we have to come up with a sort of peaceful coexistence of programs that enables everybody and supports individual investigator initiated [research].”

This mixture of the concerted large-scale programs with the insights of the investigator-initiated projects is what will allow science to turn cancer into a disease that, if not cured, can be made livable.

“Cancer is digital, it’s knowable, it’s information,” she said. “Once we digitize cancer, which is what we’re doing with the Cancer Genome Analysis, [we are] going to be able to move much more rapidly. And I think if cancer is knowable, and we can decipher all the genes that cause these cancers and make them available to everybody, that’s going to move the field exponentially.”

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