Project HOPE (High-Grade Glioma-Omics in Pediatric and AYA) and Project GBM CARE (Cellular Analysis of Resistance and Evolution) are two collaborative, intersecting research projects that use single-cell RNA sequencing to learn more about tumor heterogeneity, growth, and evolution. The projects, which are funded through the National Cancer Institute’s (NCI) Cancer Center Support Grants following advocacy from the National Brain Tumor Society and partner organizations, aim to identify commonalities in these complex tumors that can serve as new therapeutic targets and the basis for future combinations of treatments.
Tumor heterogeneity continues to represent a major challenge to successful treatment of malignant brain tumors, especially high-grade gliomas (HGG) in patients of all ages.
At the end of 2018, the National Brain Tumor Society (NBTS), working alongside the Pediatric Brain Tumor Foundation and the Eliminate Brain Cancer Initiative, led advocacy efforts that secured $4 million in funding (3P30-CA014236-47S6) from the National Cancer Institute (NCI) to grapple with this vast heterogeneity of gliomas in adult, adolescent and young adult (AYA), and pediatric populations. The push for funding stemmed from recommendations made by a diverse group of stakeholders, including researchers and patients, who participated in the inaugural U.S. Brain Cancer Mission Roundtable meeting in May 2018.
Leading neuro-oncology researchers from multiple world-class institutions came together to form the Project HOPE and GBM CARE teams. Between 2019 and 2020, the respective teams were able to establish baseline operations for transformative single-cell sequencing platforms and library prep centers, a data commons, and a tissue acquisition center. Early research has also already begun to yield results in the way of emerging patterns and early leads. In late 2020, the NCI extended the funding by $2 million total across both projects for 2021.
Single-cell sequencing approaches have emerged in recent years, providing researchers more precise information about tumors than ever before. Unlike traditional “bulk” sequencing, single-cell analysis allows the study of the various, diverse cell populations that make up a tumor and its surrounding environment. This is particularly important in highly heterogeneous tumors such as high-grade gliomas where a tumor is actually made up of many different types of cells.
“Projects Hope and GBM Care are positioned to confront the unique complexity and treatment-resistance challenges that brain tumors present. This work is critical to improving the survival rates of glioblastoma and pediatric brain tumor patients.”
– David Arons, Chief Executive Officer, National Brain Tumor Society
Bringing together leading experts from across institutions and industries, the projects address the limited availability of paired longitudinal tissue samples while employing state-of-the-art single-cell platforms to profile HGG tumors. This effort represents a first-of-its-kind research initiative spanning the pediatric, AYA, and adult HGG/GBM patient populations — from pre-treatment to post-treatment and recurrence.
Specifically, both projects will:
- 1. Perform single-nucleus RNA sequencing of malignant cells, immune cells, and non-immune microenvironmental cells in longitudinal samples of pediatric and AYA high-grade gliomas and in adult IDH-wildtype glioblastoma, pre- and post-standard of care therapy.
- 2. Create a unique Data Comms and Data Sharing platform to integrate Projects HOPE and GBM CARE results.
The projects will also collaborate with existing consortiums in neuro-oncology research, including the NBTS-funded GLASS Consortium and the Children’s Brain Tumor Network.
These analyses from the single-cell level represent a groundbreaking endeavor that will ultimately benefit and advance the entire neuro-oncology research community.
Project Coordinator: Dr. Alfred Yung, MD, MD Anderson Cancer Center
Patient Advocates: David Arons and Clair Meehan, National Brain Tumor Society
PROJECT HOPE TEAM MEMBERS
– Mariella Filbin, MD, PhD, Dana-Farber Cancer Institute
– Aaron Diaz, PhD, University of California, San Francisco
– Michelle Monje, MD, PhD, Stanford
– Adam Resnick, PhD, Children’s Hospital of Philadelphia
– Michael Prados, MD, University of California, San Francisco
PROJECT GBM CARE TEAM MEMBERS
– Mario Suva, MD, PhD, Massachusetts General Hospital and Broad Institute
– Antonio Iavarone, MD, Columbia University
– David Ashley, MD, PhD, Duke University
– Stephen Keir, DrPH, MPH, MMCi, Duke University
– Jason Huse, PhD, MD Anderson Cancer Center
– Roel Verhaak, PhD, Jackson Laboratory
– Itay Tirosh, PhD, Weizmann Institute of Science
Both research groups include two tissue procurement centers, two single-cell library prep centers, and a data commons where all data is collected and coordinated.