Deciphering METAstasis of lung cancer to BRAIN and developing new therapeutic approaches via a human metastatic cascade platform
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.
