Soft Hydrogel 3D Model for Chemotherapy-Resistant Glioblastoma CSR Project

Targeting chemotherapy-resistant aggressive recurrent glioblastoma using soft hydrogel biomaterials

Objective

• it is proposed to develop an engineered in vitro 3D model of GBM dormancy and phenotypic plasticity/heterogeneity driven primarily by the matrix through biophysical confinement. This proposed model would be a small step towards developing a platform to uncover deeper molecular insights that delineate dormant, quiescent GBM cells from proliferative, invasive populations and thereby aid in drug development for overcoming therapy-resistance in GBM.

Description

• Glioblastoma multiforme (GBM) is an aggressive subtype of brain cancer with poor survivability rate and very few established treatment strategies. In spite of advances in chemotherapy, the chances of tumor recurrence is high and majority of mortality cases are due to therapy-resistance. To study the mechanistic role of the TME on cancer cell plasticity, dormancy, and therapy resistance, it is necessary to develop reliable and predictive pre-clinical models.

Impact

• 1) Establishment of the hydrogel-based model of GBM chemoresistance with biological validation., 2) Proof-of-concept validation of GBM dormancy, recurrence and reactivation, 3) Cellular/molecular differentiation between dormancy and proliferative GBM populations, 4) Pharmacological inhibition and drug-screening studies of candidate compounds for assessing anti-cancer efficacy