Insulin Signaling & Hypoxic Response in Brain Cancer
Lin, Ka Wai
Qutub, Amina A
Doctor of Philosophy
Glioblastoma patient survival rate has stagnated for the past 30 years, with median survival time less than 1 year. Only 20% of the young (0-19 years old) glioblastoma patients survive past 5 years, and this number drops to just less than 5% for patients above 40 years old. Due to poor survival rate of glioblastoma patients, there is a pressing need to develop more effective treatment methods. In this project, we investigated the effects of the insulin signaling pathway on the glioblastoma growth. Glioblastoma growth has been shown to be promoted by three key molecular signaling factors: IGFI, IGFBP2 and HIF1α. We used both the current literature data and our own experimental data to understand the interactions between these molecular factors on glioblastoma growth via a mathematical model. The model predicted that the activation of HIF1α by IGFBP2 is a crucial driver in the glioblastoma growth. We then used in vitro experiments to validate the findings of the model, and to further explore the response of glioblastoma progression by the stimulation of IGFBP2 and IGFI. This research demonstrates how IGFI and IGFBP2 influence glioblastoma growth, and suggest that future research should investigate the effects of both IGFI and IGFBP2 to control the glioblastoma progression system as a whole.
Glioblastoma; Computational Modeling; Insulin Signaling; Hypoxic Response