Modeling the Synergistic Effect of Combination Therapy for Glioblastoma Multiforme

Open Access
Author:
Browe, Matthew Alexander
Area of Honors:
Chemical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Antonios Armaou, Thesis Supervisor
  • Wayne Roger Curtis, Honors Advisor
  • Andrew Zydney, Faculty Reader
Keywords:
  • glioblastoma
  • combination therapy
  • radiation
  • haptotaxis
Abstract:
The Vital-Lopez model of a glioblastoma multiforme (GBM) tumor was modified to include haptotactic migration strategies and radiotherapeutic treatment methods. Haptotactic incorporation strategies showed little improvement in overall tumor growth and likely involve further modification with the parameters describing the dynamics of the coupled effects of extracellular matrix degradation and repair. Radiotherapy methods were analyzed against typical fractionation schemes with and without quiescent cell killing assumed and the model was tested against fractionation schemes in vivo as well. Assumption of quiescent cell killing provided the greatest fidelity with other models but did not accurately depict high-fractionation schemes. Lastly, analysis of the model against combination therapies in vivo confirmed a synergistic effect with concomitant temozolomide and radiotherapy and provides a template for future work investigating specific synergism parameters.