This project is a game-changer in GBM research, taking a unique approach by focusing on how GBM tumours perceive their environment and how this perception contributes to their aggressive nature. The team has engineered a platform that allows researchers to examine how specific environments influence tumour behaviour. This leads to the creation of more representative models, enabling us to study the tumour in conditions that closely mimic its native environment, thereby facilitating optimal drug development.

It’s widely recognized that therapeutic development for GBM has stagnated partly due to the use of preclinical models that do not accurately represent native tumour conditions. This project addresses this issue head-on by engineering and utilizing more informative models that better mimics the conditions of actual brain tumours. The development of more informative brain cancer models will enhance the reliability of preclinical drug testing, providing more accurate indications of a therapy’s effectiveness in a clinical setting.

Glioblastoma (GBM), a lethal adult brain cancer, exhibits phenotypic plasticity, allowing it to adapt and evade therapeutic interventions. This project aims to understand and target GBM’s plasticity to develop effective therapeutic strategies. The interplay between GBM’s mechanosensory responses to its microenvironment and its ability to transition into a stem cell-like state is proposed as a survival mechanism. The project aims to fabricate and implement defined and modular microenvironments to unravel the intricate interplay between the tumours microenvironment and Glioblastoma behaviour. Using engineered brain matrix mimetic in vitro models, the research will dissect the mechanisms underlying GBM transition between different cellular states. The goal is to discover key molecular players that can serve as potential targets for future drug development.

The overarching aims of this grant includes:

Aim 1: Determine how mechanical cues guide GBM plasticity.

Aim 2: Dissect mechanotransduction pathways that regulate phenotypic plasticity.

Aim 3: Screening drugs for GBM plasticity within organs-on-a-chip.