A better way of treating brain metastases
How we treat cancer continues to advance, leading to improved outcomes, increased survival rates and a better quality of life for patients. However, one area that continues to challenge oncology is brain metastases originating from melanoma, breast and lung cancers. “These secondary brain tumours are notoriously difficult to treat due to the unique barriers of the brain microenvironment and the limited predictive value of standard 2D models,” says Ronit Satchi-Fainaro(opens in new window), a professor of Cancer Research and Nanomedicine at Tel Aviv University(opens in new window). Addressing this challenge is 3DBrainStrom(opens in new window). The EU-funded project is developing physiologically relevant 3D preclinical models, along with advanced nanomedicines, designed to overcome the biological hurdles of the brain metastatic niche. “By providing physiologically relevant platforms that better reflect human disease, we aim to enable more accurate drug testing and biomarker discovery, reduce the need for animal testing, and lay the groundwork for the effective, patient-informed treatment of brain metastases,” adds Satchi-Fainaro, who serves as the project coordinator. The project received support from the European Research Council(opens in new window) (ERC).
Recreating the architecture and dynamics of brain metastases
Using state-of-the-art 3D bioprinting, organotypic brain cultures, and microfluidic tumour-on-a-chip platforms, the project recreated the architecture and dynamics of brain metastases more faithfully than traditional 2D systems. Using these models, researchers were able to study how tumours interact with blood vessels and immune and glial cells. What they discovered were new molecular vulnerabilities in brain metastases, including the metabolic role of the p53-SCD1 axis (‘Nature Genetics’ 2025) and the immune-modulating CCL2/CCR2 pathway (‘JCII’ 2022, ‘Brain’ 2025, ‘ADDR’ 2024). “This discovery could allow us to repurpose existing drugs targeting these pathways for treating brain metastasis,” explains Satchi-Fainaro.
Using nanoparticles to selectively deliver drugs to brain tumours
The project also demonstrated a validation of radiation-induced vascular targets for the enhanced delivery of polymer-based nanoparticles (NPs) capable of selectively delivering drugs to brain tumours. According to Satchi-Fainaro, this work led to the development of dual-drug NPs and an image-guided therapy system. Both have proved to be highly efficient in preclinical brain metastasis models. “These therapeutic modalities were able to cross the blood-brain barrier and target tumours with precision in animal models,” she notes.
Turning a terminal diagnosis into a manageable chronic condition
These findings, together with the suite of precision nanomedicines developed by the project, represent a major step towards a more effective, targeted and personalised treatment of brain metastases. “I am hopeful that our work will help transform brain metastases from being a terminal diagnosis into a manageable chronic condition – ultimately improving survival and quality of life for patients facing these devastating cancers,” concludes Satchi-Fainaro. Not only has the project laid the foundation for an 80-patient clinical trial to validate the 3D platform, it has also paved the way towards additional research, including the ERC Proof of Concept grant(opens in new window) ImmuNovation project and the European Innovation Council(opens in new window) (EIC) funded TIMNano project, both of which will help turn 3DBrainStrom’s work into a precision oncology toolset.
