Profiling the Transcriptional Heterogeneity of Diverse Pediatric Solid Tumors
Lay Summary: Pediatric solid tumors arise during the development of diverse tissues such as bone, muscle and adrenal gland. The tumor cells maintain many features of the normal tissue where they develop including the developmental hierarchy. As a result, cells within an individual patient's tumor has features of different developmental stages. This tumor heterogeneity is important because, in some patients, a subset of those cells survive treatment and contribute to disease relapse which is often fatal. Single-cell profiling is essential to understand the tumor heterogeneity at diagnosis and after treatment and the interactions between tumor cells and normal cells in the tumor microenvironment.
Lay Summary Project Goal: The goal of this research proposal is to provide a comprehensive atlas of the heterogeneity across 21 different pediatric solid tumor types and their matched orthotopic xenografts. The xenografts recapitulate the heterogeneity of the patient tumors and are ideal laboratory models to gain a deeper understanding of how the populations of tumor cells change as a result of treatment. This is important because a rare subset of tumor cells can survive treatment in some patients and contribute to cancer relapse. Unfortunately, patients with relapsed solid tumors have overall survival rates of below 30%. Therefore, our long-term goal is to use the single-cell atlas to develop better therapies to kill all the tumor cells, not just the most abundant one.
