Novato’s Buck Institute part of study showing new way of classifying cancer

Researchers at Novato’s Buck Institute participated in a study culminating a 10-year, $300 million government-funded effort described as “rewriting the book” on cancer and pointing to new ways to treat the disease expected to strike 1.7 million Americans and cause more than 600,000 deaths this year.

The study’s ultimate product, called the PanCancer Atlas and published Thursday as a collection of 27 papers in several academic journals, was based on state-of-the-art technology and analysis that determined the genetic and molecular makeup of more than 10,000 tumors representing 33 types of cancer.

Scientists involved in the study said it overhauled the century-old classification of the nation’s second-leading cause of death.

“It will turn the whole science of cancer treatment on its head,” said Christopher Benz, a founding faculty member at the Buck Institute who has been involved in both research and treating breast cancer patients for nearly four decades.

Cancer, a group of diseases involving abnormal cell growth and their uncontrolled spread, has long been classified - and treated - based on its anatomical site of origin, such as the lungs, breast, kidney, prostate, pancreas and bladder.

But the PanCancer Atlas, based on a molecular analysis of the DNA, RNA and protein from each of the 10,000 tumors, reclassified the 33 anatomical types of cancer into 28 different types, or clusters, based solely on their molecular architecture.

Most importantly, Benz said, the new classification revealed that nearly two-thirds of the clusters were heterogeneous in their tumor composition, meaning they contained diverse cancers originating from as many as 25 different sites in the body.

One cluster contained 762 individual tumors arising from either the stomach, pancreas, lung, breast, bladder or from 20 other anatomical sites.

The implications for cancer therapy, he said, are revolutionary.

Treatments should target “a specific molecular abnormality” rather than the established approach of treating all cancers arising from the same site the same way, Benz said.

“We should probably be treating bladder cancer in at least four different ways,” he said, citing one example.

Moreover, an important similarity between the 25 different cancers found in a single heterogeneous cluster was the patients’ common immune system response to the diverse tumors, Benz said, indicating that immunotherapies may eventually be matched to different cancers that have a common genetic structure.

The atlas gives oncologists - and patients - a road map to future treatments that could replace conventional chemotherapy, which uses relatively unselective toxins to attack each tumor’s rapidly dividing cells.

Benz, who recently moved to Petaluma, is a professor of cancer and developmental therapeutics at the Buck Institute for Research on Aging and a clinical oncologist at UC San Francisco.

Francis Collins, director of the National Institutes of Health, which funded research for the atlas, said in a press release it was “the culmination of more than a decade of groundbreaking work.”

“This analysis provides cancer researchers with unprecedented understanding of how, where and why tumors arise in humans, enabling better informed clinical trials and future treatments,” he said

Benz, who has been part of The Cancer Genome Atlas Research Network since its inception, said “patients will have the best shot at successful treatment if their tumors can first be classified according to their genomic and molecular makeup.”

Unfortunately, that’s out of reach for most people because the molecular analysis costs tens of thousands of dollars and is not routinely covered by insurance because its medical efficacy and clinical benefit have not been proven.

The network, which involved about 150 researchers at more than two dozen institutions across North America, is now disbanding.

Among other projects, Benz’s lab at the Buck Institute is continuing to work with a team led by Josh Stuart, a professor of biomolecular engineering at UC Santa Cruz, to identify more “user-friendly” clinical tests that will align with the atlas’ newly defined molecular classification of cancer.

Meanwhile, he said, oncologists can use the atlas to help encourage patients to participate in emerging clinical studies known as “basket trials” that will better match the molecular makeup of their tumor with a new cancer drug that targets that specific cancer mechanism.

The papers comprising the PanCancer Atlas are available through a portal on cell.com

You can reach Staff Writer Guy Kovner at 707-521-5457 or guy.kovner@pressdemocrat.com. On Twitter @guykovner.