In META-BRAIN Project Nur MUSTAFAOGLU and her team aim to establish a human-based in vitro platform that comprehensively replicates the journey of cancer cells from the lungs to the brain. This platform will be instrumental in addressing three pivotal questions: (1) What is the mechanism by which cancer metastasizes to the brain? (2) What role does the blood-brain barrier (BBB) play in cancer metastasis to the brain? and (3) How and when can we effectively treat cancer metastasis? By creating a physiologically relevant human cell-based model, META-BRAIN will, for the first time, delineate the entire cascade of cancer metastasis and enable the exploration of novel target proteins at the blood-tumor barrier (BTB). Additionally, this model will serve as the foundation for developing innovative shuttle systems designed for drug delivery to the brain.
MUSTAFAOGLU's project proposal was supported within the scope of TÜBİTAK's ERC Principal Investigator Advancement Program (EBAG)
This project has become the first one supported from Turkiye in the "LS9 - Biotechnology and Biosystems Engineering" panel.
Call: ERC-2023-StG
Project Duration: 5 year
Project Acronym: META-BRAIN
Project Titleı: Deciphering METAstasis of lung cancer to BRAIN and developing new therapeutic approaches via a human metastatic cascade platform
Project ID: 101116521
Host Institution: Sabancı ÜUniversity, Türkiye
Panel: LS9 - Biotechnology and Biosystems Engineering
Related ERC Proof of Concept Project: -
Human-based in vitro platform targets understanding metastases to the brain
Lung cancer is a leading cause of death worldwide and brain metastases are a common progression. Although life expectancy is improving, the median survival rate for people whose lung cancer spreads to the brain is about 1 year. The ERC-funded META-BRAIN project aims to create a human-based in vitro platform to investigate the cancer cell journey from lung to brain that can also be used to address the role of the blood–brain barrier in cancer metastasis to the brain. It will not only help answer mechanistic questions about such metastases but potentially point the way to new diagnostics and therapeutics, including nanoshuttle systems to target proteins in brain tumours.
Objective
Brain metastases have a poor prognosis and are associated with a high morbidity and mortality rate in cancer patients. The metastatic pathways and the role of the blood-brain barrier (BBB) during metastasis are not known. There is a need to better understand cancer brain metastasis and develop effective therapeutics. With META-BRAIN, I will create a human-based in vitro platform that spans the entire cancer cell journey from lung to brain and use it to address three key questions: (1) How does cancer metastasize to the brain? (2) What is the role of the BBB in cancer metastasis to the brain? and (3) How and when can cancer metastasize be treated? The META-BRAIN will provide answers to these questions by developing a truly physiologically relevant human cell-based model, that for the first time, maps the entire cancer metastasis cascade and that can also be used to study novel target proteins at the blood-tumor barrier (BTB). This model will also be used to develop novel shuttle systems for drug delivery to the brain. By integrating state-of-the-art technologies from life sciences and engineering, META-BRAIN has three main objectives: (1) Develop an in vitro model that recapitulates the metastatic cascade with in vivo-like morphology and function to study how cancer metastases to the brain, (2) Investigate the role of extracellular vesicle (EV) and circulating tumor cell (CTC) migration events with a focus on their interactions with brain endothelia, and (3) Identification of novel target proteins specific to cancerous brain and development of novel nano-shuttle systems targeting these proteins to deliver therapeutics to the brain. In summary, META-BRAIN will lead the way in the development of physiologically relevant models for other brain-invasive metastatic cancers, open new avenues for the development of therapeutic and diagnostic approaches and pave the way for nano-shuttle formulations specifically designed to overcome the BBB and BTB.
(Resource: CORDIS)
