UC Irvine

Glioblastoma is the most lethal and prevalent form of cancer to the central nervous system. Median life expectancy for patients is five years, and in that time the tumor evolves rapidly while modifying its microenvironment in the process. When targeted with radiotherapy it increases its fraction of cancer stem cell population, thereby increasing its resistance to radiation. Recent evidence suggests that the underlying process of de-differentiation, whereby more differentiated cells return to a stem-like state, also drives recurrence. By modeling proliferation, differentiation, de-differentiation and the response to radiotherapy, this model identifies the types of feedback consistent with an increase in CSC fraction and tumor size after radiotherapy, as well as a potential radiotherapy schedule by which treatment can improve upon conventional radiotherapy scheduling. The mechanisms identified are the application of treatment, the process of de-differentiation, and the existence of negative feedback on differentiated cell division rates or positive feedback on differentiated cell death is consistent with these outcomes.