Four Groups Win CRUK “Grand Challenge”

Cancer Research UK (CRUK) has announced the winners of its first “Grand Challenge” competition, in which investigators from around the world were invited to propose novel approaches to unsolved problems in cancer research. Based on the quality of the entries, the judges awarded between £15–£20 million, or $19–$25 million, over 5 years to each of four winning teams, instead of one as was originally planned.

“We were bowled over by the insight, creativity, and advances these teams had already made in putting their proposals together,” says Edward Harlow, PhD, professor of biological chemistry and molecular pharmacology at Harvard Medical School in Boston, MA, and a member of the Grand Challenge advisory panel that reviewed the proposals. “They offered us new ways of thinking about problems in cancer that were quite exhilarating.”

For example, two teams will focus on the challenge of how to map tumors in greater detail at the cellular and molecular level by using advanced imaging technologies, including mass spectrometry and cytometry, as well as virtual reality headsets. The contest drew a total of 56 applicants, each addressing one of seven challenges (Cancer Discov 2016;6:7–8).

Following are brief descriptions of the four winning proposals, which will receive a combined total of over £70 million, or about $87 million:

• Studying cancer-associated mutational fingerprints to attain a deeper understanding of what causes DNA damage, how it leads to cancer, and whether the damage can be prevented (led by Sir Michael Stratton, PhD, of the Wellcome Trust Sanger Institute in the UK)

• Analyzing tissue samples taken from women with ductal carcinoma in situ to identify biomarkers of breast cancer (led by Jelle Wesseling, MD, PhD, at the Netherlands Cancer Institute in Amsterdam)

• Using mass spectrometry imaging to create detailed maps of the entire molecular makeup of breast, bowel, and pancreatic tumors (led by Josephine Bunch, PhD, at the National Physical Laboratory in the UK)

• Creating 3-D models of breast cancer that can be studied using virtual reality headsets (led by Gregory Hannon, PhD, at the University of Cambridge in the UK)

The winning investigators will collaborate across many geographic borders and fields of study. The 14-member team led by Hannon, for example, draws upon the combined expertise of molecular biologists, astronomers, and game developers from the UK, Switzerland, the United States, Canada, and Ireland.

Hannon's team will focus on creating “extremely faithful, anatomical models of tumors with deep molecular annotation,” says Hannon. “Our initial goal is to study the 10 subtypes of breast cancer previously described, and collect enough tumors from each subtype to establish patterns that occur within the subtypes and across multiple incidences of the disease.”

They have already started collecting thousands of pieces of information about every cell in a tumor to discover exactly where cells are positioned, he explains. Using tissue samples from women involved in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) study, they will annotate entire transcriptomes—or all of the RNA contained in a cell (Nature 2012;486:346–52). They will also use mass cytometry coupled with approximately 50 metal-tagged antibodies to study the location and abundance of proteins in a tumor.

The team has already created a prototype that allows scientists to experience—via virtual reality headsets—what it's like to walk around inside a breast tumor and to observe how individual cells interact and influence each other.

“Virtual reality allows us to ‘fly’ inside a tumor and look at every cell,” Hannon explains. “We are able to see whether the same cell types behave differently depending on where they are located in the tumor and to recognize patterns and characteristics that are very difficult to see in 2-D.”

Ultimately, says Hannon, the goal of the research is to create a blueprint for studying all types of tumors that can be used in the clinic for education and diagnostic purposes.

“We will try to capitalize on the multiuser experience developed by the video game industry to put researchers, doctors, and patients in the same virtual space at the same time,” he says. “Our ultimate dream is that this becomes part of modern molecular pathology.” –Janet Colwell

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