Modeling Group 3 Medulloblastoma: Describing the Interconnected Pathway of the Most Common Pediatric Brain Cancer

Author

Amber Cantú, William & MaryFollow

Date Thesis Awarded

5-2024

Access Type

Honors Thesis -- Open Access

Degree Name

Bachelors of Science (BS)

Department

Neuroscience

Advisor

Randolph A. Coleman

Committee Members

Christy Porter

Jorge Terukina

Abstract

Group 3 medulloblastoma is one of the most common pediatric brain cancers. Affecting infants and children, this cancer has the worst prognosis of the medulloblastoma group. Current treatments use surgical resection, radiation, and chemotherapy to afflict the cancer, however no cure has been found. This project aims to model one of the many pathways being investigated in Group 3 medulloblastoma which may be used to synthesize future treatments. Specifically, showing the interconnections between various precursors of BCL-xL, an antiapoptotic protein, and how these factors influence the progression of the disease. Scientific databases were used to find previous research articles which were analyzed for qualitative and quantitative information. In silico modeling and simulation of biochemical processes were performed by CellDesigner and COPASI, respectively. These methods were used to represent and quantify the overall pathway. It was found that BCL-xL inhibits the formation of the BAX pore and is modulated by NRL and its precursors OTX2 and CRX as well as the IL-6 pathway. This project shows that increased concentrations of intracellular OTX2, NRL, CRX, and IL-6 lead to increased BCL-xL concentrations and promote BCL-xL binding with the BAX pore subunits, inhibiting apoptosis. This pathway supports previous hypotheses for Group 3 medulloblastoma cancer cell progression by modeling the biochemical pathway that prevents cell death. Interestingly, an external factor that has been found to possibly influence this pathway is maternal diet. Lastly, potential treatments that aim at shunting the progression of the pathway by inhibiting precursors to the antiapoptotic protein BCL-xL were discussed.

Recommended Citation

Cantú, Amber, "Modeling Group 3 Medulloblastoma: Describing the Interconnected Pathway of the Most Common Pediatric Brain Cancer" (2024). Undergraduate Honors Theses. William & Mary. Paper 2149.
https://scholarworks.wm.edu/honorstheses/2149

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