Single-Cell RNAseq-Directed Targeting of Therapy-Resistant Subpopulations That Drive Relapse in Childhood Ependymoma
Abstract
A review of the new Fiscal Year 2019 (FY19) Peer Reviewed Cancer Research Program (PRCRP) Topic Areas reveals pediatric brain tumors as a focus area. My proposed research addresses this critical topic area through the development of an effective therapeutic strategy to treatment ependymoma, a pediatric brain tumor that carries a high risk of recurrence and death. Ependymoma is fatal in over 50% of children and has not seen any therapeutic improvements in over 30 years, despite numerous clinical chemotherapy trials. The most recent Children’s Oncology Group (COG) clinical trial in ependymoma suggests that posterior fossa A ependymoma subgroup tumors, particularly those with a gain of the long arm of chromosome 1 are at very high risk of death. In the past decade our understanding of the biology of ependymoma has greatly advanced. Despite advances in biological characterization of ependymoma, the underlying complexity of cells within all ependymoma tumors is an obstacle to advancing our understanding of the biology of these tumors. This is a roadblock in development of effective therapies for children with ependymoma. In an effort to tackle this problem, our laboratory has used cutting edge technology to define the biology of ependymoma at the single-cell level, called single-cell RNA sequencing (scRNAseq). The powerful scientific approach has already significantly advanced our biological understanding of childhood ependymoma, identifying diverse types of cells within each tumor some of which are associated with a worse patient survival. We next identified features of the more aggressive cell types that can potentially be targeted by currently available Food and Drug Administration-approved chemotherapy drugs. Our proposed study intends to fully test these promising chemotherapy agents in the laboratory using novel human cell lines and animal models of childhood ependymoma that we have developed over the past 5 years. The results of these innovative single cell focused chemotherapy studies will directly impact future clinical trials of childhood ependymoma. This research has the potential to help military Service members and their families. Ependymomas affect children and adolescents, but have also been found in older adults, making the results of my studies apply beyond the pediatric population. They could therefore directly affect therapy for our military Service members. Also, with the destructive effects a life-threatening illness in a child can have on the entire family, not only on the direct Service member, improving the care of these patients by both increasing their chance of survival can benefit everyone effected by the disease, not just the patient.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010672
Entities
People
- Nicholas K Foreman
Organizations
- United States Army
- University of Colorado Denver