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Systematic Review of Pre-Clinical Systems Using Artificial Microenvironments and Anti-Migratory Drugs to Control
Hana Selvi1, Anke Brüning-Richardson2, Davide Danovi1,3,4
1Centre for Gene Therapy and Regenerative Medicine, King's College London, London, United Kingdom.
Background:
Glioblastoma multiforme (GBM) is the most prevalent primary brain tumour, with an incidence of 2 per 100,000. The standard clinical treatments do not sufficiently target cell migration and invasion, leading to recurrence after surgical resection and resistance after chemotherapy and radiotherapy. Pre-clinical studies are being conducted to construct artificial substrates that can mimic the tumour microenvironment (TME) to prevent GBM cells from migrating along their primary route through blood vessels and white matter tracts. Alongside, targeted therapies using anti-migratory or ‘migrastatic’ drugs are also being developed. This study aimed to review the therapeutic translational strategies emerging from the study of the GBM microenvironment and anti-migratory drugs.
Methods:
A systematic literature search was carried out using search key terms and synonyms. Full-paper screening was performed based on specific inclusion and exclusion criteria.
Results:
From the systems interrogated, the ‘Nanofibre’ assay is suitable to simulate white matter tracts, while hydrogel-based invasion assays and GBM cerebral organoid (GLICO) mimic the brain extracellular matrix. Inhibitors with anti-migratory activity found in this study are active involving distinct molecular mechanisms and have been tested on cell migration assays.
Conclusion:
Overall, we have analysed therapeutic strategies emerging from an artificial GBM TME approach and from the identification of anti-migratory inhibitors. Both carry potential to improve treatment options to prevent tumour dissemination and spread for GBM.
Insights
New therapeutic strategies for glioblastoma multiforme (GBM) involve artificial tumor microenvironments (TME) and anti-migratory drugs. These approaches show promise in preventing GBM cell invasion and spread.
Area of Science:
- Neuro-oncology
- Biomedical Engineering
- Pharmacology
Background:
- Glioblastoma multiforme (GBM) is the most common primary brain tumor.
- Current treatments fail to adequately address GBM cell migration and invasion, leading to recurrence and resistance.
- Pre-clinical research focuses on artificial tumor microenvironments (TME) and anti-migratory drugs to combat GBM spread.
Purpose of the Study:
- To review emerging therapeutic translational strategies for GBM.
- Focus on approaches utilizing artificial GBM TME and anti-migratory inhibitors.
Main Methods:
- Systematic literature search using defined keywords and synonyms.
- Full-paper screening based on specific inclusion and exclusion criteria.
Main Results:
- Nanofiber assays simulate white matter tracts; hydrogel assays and GBM cerebral organoids (GLICO) mimic the brain extracellular matrix.
- Identified inhibitors with anti-migratory activity target distinct molecular mechanisms and have been validated in cell migration assays.
Conclusions:
- Artificial GBM TME models and anti-migratory inhibitors represent promising therapeutic avenues.
- These strategies have the potential to improve treatment outcomes by preventing tumor dissemination and spread in GBM.
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