St. Jude Children’s Research Hospital and two of the nation’s other leading cancer research institutions have formed the largest academic collaboration of its kind to transform and accelerate the identification of vulnerabilities in pediatric cancers and translate them into better treatments for children worldwide.
For St. Jude, the project is part of a historic, $12.9 billion strategic plan to accelerate research on the toughest cancers with an increased focus on curing childhood cancer worldwide. That record investment, over six years, is funded by donors.
Work already was underway by the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute to understand and map vulnerabilities in adult and pediatric cancers and translate them into better treatments. St. Jude joined with Broad and Dana-Farber for a new project focused on pediatric cancers by all three institutions of more than $60 million over five years. This investment will support infrastructure development and scientific work by a team currently composed of more than 80 collaborating investigators, data scientists and research staff. The effort is expected to reach 100 members as each institution adds employees.
The newly announced collaboration with Broad and Dana-Farber combines the intellectual leadership, technical expertise and institutional resources of the three institutions. It is designed to address critical gaps in knowledge related to the biological basis of childhood cancer, and how it might more effectively be treated. Known as the Pediatric Cancer Dependencies Accelerator project, the collaboration is notable for its large scale of investment, number of collaborating scientists and scientific scope, and will accelerate progress in the development of new treatments for aggressive childhood cancers.
“Despite many advances, cancer remains the number one cause of death by disease for children in the U.S.,” said Charles W.M. Roberts, MD, PhD, the St. Jude Comprehensive Cancer Center director who co-leads the collaboration. “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.”
Other co-leaders are Francisca Vazquez, PhD, Broad Institute Cancer Dependency Map Project director and Kimberly Stegmaier, MD, physician, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and vice chair of Pediatric Oncology Research at Dana-Farber.
"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. I am excited to see the impact this project will have on the pace of therapeutic discovery for pediatric tumors.”
“Our first-generation Pediatric Cancer Dependency Map project was wildly successful but just the tip of the iceberg,” Stegmaier said. “I am so excited about this unprecedented collaboration among three extraordinary institutions. 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.”
The collaboration has several specific objectives:
• 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 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.
• Developing computational approaches to mine and integrate data and developing innovative software tools for data sharing.
The collaboration builds on groundbreaking research initiatives from each institution. Over the past decade, the St. Jude-Washington University Pediatric Cancer Genome Project and other large-scale sequencing efforts have yielded rich insights into the genomic landscape of pediatric cancers, including the understanding that most disease-driving genetic mutations are not druggable. Developing precision therapies will require identifying cancer dependencies and vulnerabilities that are not revealed by mining genomic datasets alone.
The Cancer Dependency Map (DepMap) Initiative at Broad has developed extensive, world-class 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. For example, whole-genome CRISPR screens, a technology that enables scientists to systematically turn off every single gene one-at-a-time in cancer cells to find the genes that when turned off will selectively kill the cancer, have now been effectively deployed at scale to identify vulnerabilities in hundreds of adult cancers. Proof of principle has been established that these approaches can also identify weaknesses in childhood cancers, which often have much simpler genomes. Large-scale drug screening capabilities have also been developed. That infrastructure and expertise will be leveraged and expanded through this effort.
The project will rely on expertise from St. Jude and Dana-Farber in the creation of patient-derived models that use cancer cells derived 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 a breadth of expertise on the analyses of epigenomic and genomic characterizations, data visualization and the development of computational pipelines. Epigenomics is a field in which researchers chart the locations and understand the functions of all the chemical tags that mark the genome.
St. Jude, Broad and Dana-Farber investigators will work together in groups to focus on three core disease areas (brain tumors, hematological malignancies and solid tumors) and bring to bear pan-cancer expertise in data science, functional genomics and large-scale drug screening. Together, researchers at these institutions will enhance and accelerate progress by combining unique strengths and resources to address the greatest challenges to understanding and treating pediatric cancers.