Center for Precision Medicine for High-risk Pediatric Cancer Research Overview

Adam Resnick, PhD, is co-leader of the NIH-supported Center for Data-Driven Discovery in Biomedicine (D3B) initiative which is supporting DNA methylation analyses of >3,500 brain tumor samples. These large-scale research-based data are being hosted on CHOP’s NIH-supported cloud-based genomic platforms where data are both stored, processed, harmonized and interpreted at scale while providing rapid access to such harmonized data across CHOP's Research Institute community. Research sequencing efforts have been further complemented by recent clinical and diagnostic sequencing efforts at CHOP with RNA fusion and multi-gene DNA-based panels.

In these initial studies, we showed that clinical testing at CHOP had a critical impact on clinical care in 78.7% of patients, including refining diagnosis, prognosis, and/or treatment planning. Together, such large-scale, multi-omic biospecimen-derived foundational data generation, combined with clinical imaging and outcome data, as supported by leading edge cloud-based informatics platforms, remain unprecedented in the pediatric cancer setting. These set the stage for breakthroughs which will implement automated longitudinal electronic health record clinical data extraction to substantially increase the utility of this sequencing data for discovery of novel biomarkers and therapeutics and incorporate clinical decision support tools to leverage this research to enhance clinical care.

Kai Tan, PhD, director of the Center for Single Cell Biology, will lead the preclinical single cell profiling studies and development efforts with close input from Drs. Laetsch and Li. Under the 10-year NIH Gabriella Miller Kids First Data Resource Center initiative awarded to CHOP, investigators have recently characterized more than 14,000 brain tumors, extra cranial solid tumors, and leukemia/lymphoma samples via whole genome sequencing and RNAseq, creating some of the largest foundational molecular datasets of their kind in pediatric cancer. Through an NCI Moonshot initiative grant, Dr. Tan, in collaboration with Stephen Hunger, MD, leads the Center for Pediatric Tumor Cell Atlas to map molecular and cellular changes in tumor microenvironment and the immune system of high-risk pediatric cancers.

Theodore Laetsch, MD, coordinating PI of the Center for Precision Medicine in High-risk Pediatric Cancer and director of the Developmental Therapeutics Program will leverage his experience in molecularly targeted therapies/precision medicine and early phase clinical trials to lead the precision medicine clinic and proposed clinical trial development. Demonstrating the translational feasibility of precision medicine approaches are a total of 40 active precision medicine studies open across all sections in the Center for Childhood Cancer Research, including CHOP-physician led multi-site/international studies, consortium studies, and industry-sponsored trials. This Frontier Program we will expand our ability to conduct more investigator-initiated trials at CHOP and speed clinical translation of laboratory discoveries to expedite the impact of CHOP’s laboratory research, tumor sequencing and biomarker discovery.

In tandem, Marilyn Li, MD, director of Cancer Genomic Diagnostics, will build on her experience successfully implementing DNA and RNA-based clinical tumor sequencing at CHOP to clinically validate and implement methylation profiling and ctDNA testing.