Evolution of Preclinical Models for Glioblastoma Modelling and Drug Screening.

in Current oncology reports by Grace Thomas, Ruman Rahman

TLDR

  • A review of preclinical models for glioblastoma, exploring the transition from traditional to advanced organoid and microfluidic platforms, to improve drug screening and precision medicine.

Abstract

Isocitrate dehydrogenase wild-type glioblastoma is an extremely aggressive and fatal primary brain tumour, characterised by extensive heterogeneity and diffuse infiltration of brain parenchyma. Despite multimodal treatment and diverse research efforts to develop novel therapies, there has been limited success in improving patient outcomes. Constructing physiologically relevant preclinical models is essential to optimising drug screening processes and identifying more effective treatments. Traditional in-vitro models have provided critical insights into glioblastoma pathophysiology; however, they are limited in their ability to recapitulate the complex tumour microenvironment and its interactions with surrounding cells. In-vivo models offer a more physiologically relevant context, but often do not fully represent human pathology, are expensive, and time-consuming. These limitations have contributed to the low translational success of therapies from trials to clinic. Organoid and glioblastoma-on-a-chip technology represent significant advances in glioblastoma modelling and enable the replication of key features of the human tumour microenvironment, including its structural, mechanical, and biochemical properties. Organoids provide a 3D system that captures cellular heterogeneity and tumour architecture, while microfluidic chips offer dynamic systems capable of mimicking vascularisation and nutrient exchange. Together, these technologies hold tremendous potential for high throughput drug screening and personalised, precision medicine. This review explores the evolution of preclinical models in glioblastoma modelling and drug screening, emphasising the transition from traditional systems to more advanced organoid and microfluidic platforms. Furthermore, it aims to evaluate the advantages and limitations of both traditional and next-generation models, investigating their combined potential to address current challenges by integrating complementary aspects of specific models and techniques.

Overview

  • The study focuses on the development of preclinical models for glioblastoma, specifically exploring the transition from traditional models to organoid and microfluidic platforms.
  • The review aims to evaluate the advantages and limitations of various models, emphasizing their potential for high-throughput drug screening and personalized precision medicine.
  • The study highlights the importance of constructing physiologically relevant preclinical models to optimize drug screening processes and identify more effective treatments for glioblastoma.

Comparative Analysis & Findings

  • Traditional in-vitro models provide critical insights into glioblastoma pathophysiology but are limited in their ability to recapitulate the complex tumour microenvironment.
  • In-vivo models offer a more physiologically relevant context but are often expensive, time-consuming, and do not fully represent human pathology.
  • Organoid and glioblastoma-on-a-chip technology offer significant advances in glioblastoma modelling, enabling the replication of key features of the human tumour microenvironment.

Implications and Future Directions

  • The integration of complementary aspects of specific models and techniques has the potential to address current challenges in glioblastoma modelling and drug screening.
  • Future research directions include investigating the potential of next-generation models for personalized precision medicine and high-throughput drug screening.
  • The development of new therapeutic strategies and novel biomarkers will likely require the integration of experimental, computational, and clinical approaches.
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