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Science in Mind

Studies of leukemia, endometrial cancer point to new research directions

Two large research teams have produced exhaustive genomic studies that reveal the most detailed catalog yet of the mutations that drive two deadly cancers — endometrial cancer and acute myeloid leukemia. The two studies of samples taken from hundreds of patients suggest new possible drug targets and ways to divide cancers into subtypes that might respond differently to treatment.

The new data are the latest fruits of a major national effort to create an atlas of the DNA blueprints of at least 20 types of cancer. Genomic data have been churned out in the past few years for five other cancers, and more are expected.

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While the results published last week are being hailed as major technological and scientific feats that provide powerful insights into diseases in dire need of progress, they are just first steps toward the goals most patients and physicians care about: lengthening lives or curing cancer.

Dr. David Steensma, Dana-Farber Cancer Institute adult leukemia specialist, welcomed the new data, but also provided a bit of a reality check on how far the knowledge is from changing patient care, in an essay published in the New England Journal of Medicine called “The Beginning of the End of the Beginning in Cancer Genomics.”

Steensma argues that data-rich genome studies of cancer are a crucial step, but that cancer genomes are a powerful starting position in the effort to transform patient care and treat cancers more effectively.

Mapping the genomic architecture of most major cancers is “already being done or almost done,” Steensma said. “That sort of huge survey, that sort of large landscape of what’s actually mutated in these tumors is going to be done within a year or two for all the common tumors, all the really big killers. . . . So we’re getting to the end of that first era.”

Steensma draws an analogy to 1803, when explorers Meriwether Lewis and William Clark began preparing to map the West. The cancer genome atlas, Steensma argues, is like that first exploration of unknown territory.

But that initial survey was just the beginning. Today, when property is sold, land surveyors still go out and denote boundaries; what were once the tools of discovery are now used in everyday transactions.

Steensma foresees the same thing happening as knowing the genomic landscape of the tumors is integrated into the clinic.

Steensma views the new data as a boon that might help alter a depressing state of affairs in his field, in which treatment of acute myeloid leukemia hasn’t changed from a chemotherapy regimen that was developed when he was a boy playing Little League in the 1970s.

“There have been more than 30 trials trying to improve on that, and nothing has been shown to be better,” Steensma said. He says the new data point to new therapeutic strategies that could be tried and novel ways to partition patients into groups.

The study of endometrial cancer, published in the journal Nature, similarly opens up new research avenues, said Raju Kucherlapati, a professor of genetics at Harvard Medical School and Brigham and Women’s Hospital and a co-author of the study.

Endometrial tumors are often classified based on the types of cells in the tumor and traditional pathological examination of the tissue. What the new study suggests, Kucherlapati said, is that a more effective way of classifying the disease would be to use genetic measures to classify the drivers of the disease, such as the number of extra copies of stretches of DNA.

“The next step is the people who are really clinical people or oncologists have to step up now and take this information, and use this information, to conduct clinical trials with these new approaches,” Kucherlapati said.

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