Considerations for modelling diffuse high-grade gliomas and developing clinically relevant therapies
Sarah L Higginbottom1,2, Eva Tomaskovic-Crook3,4,5, Jeremy M Crook6,7,8
1Intelligent Polymer Research Institute, AIIM Facility, Innovation Campus, University of Wollongong, Fairy Meadow, NSW, 2519, Australia.
Abstract:
Diffuse high-grade gliomas contain some of the most dangerous human cancers that lack curative treatment options. The recent molecular stratification of gliomas by the World Health Organisation in 2021 is expected to improve outcomes for patients in neuro-oncology through the development of treatments targeted to specific tumour types. Despite this promise, research is hindered by the lack of preclinical modelling platforms capable of recapitulating the heterogeneity and cellular phenotypes of tumours residing in their native human brain microenvironment. The microenvironment provides cues to subsets of glioma cells that influence proliferation, survival, and gene expression, thus altering susceptibility to therapeutic intervention. As such, conventional in vitro cellular models poorly reflect the varied responses to chemotherapy and radiotherapy seen in these diverse cellular states that differ in transcriptional profile and differentiation status. In an effort to improve the relevance of traditional modelling platforms, recent attention has focused on human pluripotent stem cell-based and tissue engineering techniques, such as three-dimensional (3D) bioprinting and microfluidic devices. The proper application of these exciting new technologies with consideration of tumour heterogeneity and microenvironmental interactions holds potential to develop more applicable models and clinically relevant therapies. In doing so, we will have a better chance of translating preclinical research findings to patient populations, thereby addressing the current derisory oncology clinical trial success rate.
Insights
Developing advanced preclinical models for diffuse high-grade gliomas is crucial. New tissue engineering and stem cell techniques can better mimic tumor heterogeneity and microenvironment for improved cancer therapies.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Biomedical Engineering
Background:
- Diffuse high-grade gliomas are aggressive human cancers with limited treatment options.
- The 2021 World Health Organization molecular classification aims to personalize neuro-oncology treatments.
- Current preclinical models fail to replicate glioma heterogeneity and the brain microenvironment, limiting therapeutic development.
Purpose of the Study:
- To highlight the limitations of conventional in vitro models for diffuse high-grade gliomas.
- To explore the potential of novel tissue engineering and stem cell-based approaches for improved modeling.
- To emphasize the importance of recapitulating tumor heterogeneity and microenvironment for therapeutic advancements.
Main Methods:
- Review of current limitations in preclinical glioma modeling.
- Discussion of emerging technologies like 3D bioprinting and microfluidic devices.
- Focus on human pluripotent stem cell-based platforms.
Main Results:
- Conventional models do not accurately reflect varied responses to therapy due to lack of microenvironmental context.
- Novel approaches using stem cells and tissue engineering offer more relevant models.
- These advanced models can better represent tumor heterogeneity and cellular states.
Conclusions:
- Improved preclinical models are essential for translating research to clinical success in neuro-oncology.
- Incorporating tumor heterogeneity and microenvironmental interactions is key to developing effective treatments for diffuse high-grade gliomas.
- Advanced modeling techniques hold promise for increasing the success rate of oncology clinical trials.
