Cancer Encyclopedia May Aid Development of Therapies

With the publication of the online Cancer Cell Line Encyclopedia—detailed in Nature last Thursday—researchers are one step closer to effective personalized cancer therapy.

The encyclopedia was a collaborative endeavor between the Broad Institute of Harvard and MIT, the Harvard-affiliated Dana-Farber Cancer Institute, and the biotech company Novartis. It catalogues data on the genetic composition of nearly a thousand cancer cell lines—about 75 percent of those commercially available, according to Levi A. Garraway, senior academic author and member at the Broad Institute and the Dana Farber Cancer Institute.

Researchers looked for and analyzed mutations and variation in epigenetic control of expression in each cell line, said Gregory V. Kryukov, a senior computational biologist at the Broad Institute and co-author of the paper.

“Working on a project of that size is exciting but can involve some unglamorous work,” said Nicolas Stransky, co-first author and lead computational biologist for the project. “Someone has to carefully check the data so that in the end we have a resource of great quality.”

The encyclopedia will be a critical resource for scientists.

“So much cancer research has been carried out in a matter agnostic to the underlying genetics,” Garraway said. “It almost seems silly that you’re doing research on a genome without even knowing what is happing to the genome.”

By treating several hundred cell lines with various drugs, researchers were able to correlate drug sensitivity to specific genetic markers in the cell lines. This will provide researchers and doctors with greater predictive power—the ability to screen tumors and prescribe medication specifically suited to the genetic composition of the tumor.

“If it were not for the great variability between human individuals, medicine may be a science and not an art,” said Kryukov. “It’s really amazing how much data we have.”

As is the case with most large projects—the CCLE is the largest collection of cell line data to date—researchers working on the project experienced logistical challenges like obtaining cell lines.

“It’s easy to get lost in the amount of data,” said Stransky. “There are thousands of samples—the project can get very complex at times—but this is where we’ve been really lucky to collaborate with extremely efficient people.”

Research for the CCLE first began in early 2008 after nearly a year of contract negotiations between the Broad Institute and Novartis.

The delay was necessary so that researchers could ensure that “data generated by us on the academic side was completely going to be publically available,” said Garraway.

Companies must maintain a greater focus on the bottom line than academic institutions, but Garraway said that overall this was an advantage.

“It kept the project going and accountable in ways that we don’t necessarily do in such a strict way academically,” he said.

In fact, multiple researchers cited the interaction between scientists at the Broad and Novartis as one of the most engaging aspects of the project.

“Being really at the middle of all these people generating data at the Broad, I could see how everyone was interacting and collaborating,” said Stransky.

Kryukov said he anticipates at least two more years of work on the project to deepen characterization of existing cell lines and test new compounds.

—Staff writer Radhika Jain can be reached at radhikajain@college.harvard.edu.

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