Little Girl with Cancer Holding her IV Pole
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In what the three institutions call the largest academic collaboration of its kind, the Broad Institute of MIT and Harvard, Dana-Farber Cancer Institute and St. Jude Children’s Research Hospital announced a five-year, $60 million to address critical gaps in knowledge related to the biological basis of pediatric cancer, and how it might be treated more effectively.

The joint funding for the project, called the Pediatric Cancer Dependencies Accelerator, will support development of infrastructure and the work of more than 80 investigators, data scientists, and associated research staff—a number that is expected to exceed 100 team members as each institution adds staff to support the work.

Cross-functional groups will focus on three core disease areas—brain tumors, hematological malignancies, and solid tumors—and will combine pan-cancer expertise in data science, functional genomics, and large-scale drug screening.

The project is co-led by Charles W.M. Roberts, MD, PhD, St. Jude Comprehensive Cancer Center director; Kimberly Stegmaier, MD, Dana-Farber Cancer Institute, vice chair of Pediatric Oncology Research; and Francisca Vazquez, PhD, Broad Institute Cancer Dependency Map Project director.

“Despite many advances, cancer remains the number one cause of death by disease for children in the U.S.,” Roberts said in a press release. “It can take decades in a research lab to understand mechanisms and develop new treatments. Through this project, we believe we can now leapfrog barriers to rapidly identify therapeutic vulnerabilities in childhood cancer and translate those into targeted therapies in the clinic much faster.”

Focused research by the Pediatric Cancer Dependencies Accelerator to develop new treatments for aggressive forms of pediatric cancer will include:

  • Developing and deploying genome editing techniques to identify hidden vulnerabilities (dependencies) in a range of high-risk childhood brain, solid, and blood cancers;
  • Leveraging emerging technologies to characterize the genetic and epigenetic landscape of pediatric cancers;
  • Developing model systems where none currently exist for high-risk childhood cancers that have poor outcomes;
  • Identifying effective combination therapies and mechanisms of drug resistance and shortening the timeline for developing new therapies; and
  • Developing computational approaches to mine and integrate data and developing innovative software tools for data sharing.

To achieve its goals, the Accelerator will combine, and build open years of groundbreaking research from each of the three institutions.

For instance, the St. Jude-Washington University Pediatric Cancer Genome Project, was a $65 million collaboration begun in 2010 to sequence the complete normal and cancer genomes of 600 pediatric cancer patients—at a time when most cancer research focused on adult subjects. When finished, the project had complete normal and cancer genomes of 800 children, and also included whole-exome and whole-transcriptome sequencing of an additional 1,200 patients, which included 23 different cancers.

But developing new, targeted treatments for pediatric cancers will require more than genomic data. The Broad’s computational expertise will be vital for the project. Its Cancer Dependency Map (DepMap) Initiative has developed extensive, datasets and computational infrastructure that has impacted research and target discovery programs worldwide. Launched in 2015, the Pediatric Cancer Dependency Map Project (PedDep) served as a proof-of-concept to apply the DepMap approach to childhood cancers.

Among the successes of the two programs at the Broad are the successful deployment of whole-genome CRISPR screening tools that have been used to find vulnerabilities in adult cancers. These also have been shown to be an effective means of interrogating the vulnerabilities of childhood cancers, which often have much simpler genomes. The works has also yielded the development of large-scale drug screening capabilities.

“The PedDep Accelerator exemplifies the power of deep collaboration and of bringing a multidisciplinary team together across institutions to tackle an important disease challenge that affects children worldwide,” Vazquez said. “Through data sharing and tool development, we are committed to creating a resource that the scientific community can leverage to make a real impact on childhood cancers.”

St. Jude and Dana-Farber will provide expertise in the creation of patient-derived xenograft (PDX) models that use cancer cells from patients, and thus more closely match the biology of the disease as it appears in the clinic. Computational biologists at St. Jude will contribute analyses of epigenomic and genomic characterizations, data visualization and the development of computational pipelines.

“Our first-generation Pediatric Cancer Dependency Map project was wildly successful but just the tip of the iceberg,” Stegmaier said. “The PedDep Accelerator will uncover novel, and much needed, new therapeutic targets while also revealing the mechanistic underpinnings of a wide range of childhood cancers, providing a treasure trove of data for our research community.”

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