An Organ-Specific In Vitro 3D Platform for Diffuse Intrinsic Pontine Glioma
Abstract
Diffuse intrinsic pontine glioma (DIPG) is a rare form of inoperable cancer arising in the brainstem of children. Most children with DIPG lose their battle with the disease within 8-11 months of their initial diagnosis, as there are no curative treatments for these tumors to date. The distinctly unique habitat of the brainstem and the invasive nature of these tumors is not adequately represented in animal models, and patient derived cancer cell lines that are routinely utilized in development of therapy for DIPG. As a result of this inconsistency between the preclinical models and the native tumor, despite promising preclinical data, the response to clinical drug trials has been dismal. There is therefore an unmet need for robust experimental models that can transform our understanding of the disease biology and be harnessed to predict response more accurately in children with DIPG. Understanding how the tumor cell interacts with its tumor microenvironment (TME), an area populated with diverse brain-specific cell types and the non-cellular tissue scaffold, is a critical step towards better understanding the disease process and advancing treatments. Leveraging our ability to grow cells in a three-dimension (3D), we have designed a novel microfluidic platform that incorporates elements of the DIPG environment enabling the DIPG cells to grow and interact with neighboring cells and the surrounding extra-cellular framework, simulating the tumor’s biology in pediatric patients. In the proposed study, this tractable and practical 3D system will allow us to accurately demonstrate and study the mechanism of how cancer cells communicate with and colonize their dynamic ecosystem. This is an important step forward, with potential to accelerate the disease management strategies for DIPG and aligns with the Fiscal Year 2021 Rare Cancers Research Program Focus Areas of developing a research model for predicting how the pediatric patients will respond to therapeutic interventions. Therapeutic investigations in a miniaturized platform capable of representing aspects of the tumor tissue will be of immediate value to academia, pharmaceutical industry, and clinicians whose research focuses on hard-to-treat and/or rare cancers and impact the indiscriminate use of mice in preclinical studies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210881
Entities
People
- Meenakshi Upreti
Organizations
- United States Army