Abstract
Early clues to tumors and their microenvironments come from embryonic development. Here we review the literature and consider whether the embryonic brain and its pathologies can serve as a better model. Among embryonic organs, the brain is the most heterogenous and complex, with multiple lineages leading to wide spectrum of cell states and types. Its dysregulation promotes neurodevelopmental brain pathologies and pediatric tumors. Embryonic brain pathologies point to the crucial importance of spatial heterogeneity over time, akin to the tumor microenvironment. Tumors dedifferentiate through genetic mutations and epigenetic modulations; embryonic brains differentiate through epigenetic modulations. Our innovative review proposes learning developmental brain pathologies to target tumor evolution-and vice versa. We describe ways through which tumor pharmacology can learn from embryonic brains and their pathologies, and how learning tumor, and its microenvironment, can benefit targeting neurodevelopmental pathologies. Examples include pediatric low-grade versus high-grade brain tumors as in rhabdomyosarcomas and gliomas.
Overview
- The study explores whether the embryonic brain and its pathologies can serve as a better model for understanding tumors and their microenvironments.
- The embryonic brain is the most heterogenous and complex among other organs, with multiple lineages leading to a wide spectrum of cell states and types.
- The study proposes learning from developmental brain pathologies to target tumor evolution and vice versa, with a focus on pediatric low-grade and high-grade brain tumors
Comparative Analysis & Findings
- The study highlights the importance of spatial heterogeneity over time in embryonic brain pathologies, which is similar to the tumor microenvironment.
- Tumors dedifferentiate through genetic mutations and epigenetic modulations, whereas embryonic brains differentiate through epigenetic modulations.
- Examples of pediatric brain tumors include rhabdomyosarcomas and gliomas, which can be compared and contrasted to learn more about their evolution and treatment options
Implications and Future Directions
- The study's findings suggest that learning from developmental brain pathologies can benefit targeting neurodevelopmental pathologies and pediatric brain tumors.
- Tumor pharmacology can learn from embryonic brains and their pathologies to develop more effective treatments.
- Future research can explore the application of this approach to other types of tumors and their microenvironments