Physical fingerprints of single extracellular vesicles for liquid biopsy in brain cancer
- Sara Mahshid, McGill University
- Janusz Rak, The Research Institute of the McGill University Health Centre
- Walter Reisner, McGill University
- Sebastian Wachsmann-Hogiu, McGill University
- Kevin Petrecca, McGill University
- Canadian Cancer Society
- Canadian Institutes of Health Research
Need for project: Glioblastoma (GBM) is an incurable brain cancer that changes rapidly confounding standard diagnostic and therapeutic methods. These changes in molecular composition can be captured by bits of cancer cells known as extracellular vesicles (EVs) found in blood of patients (liquid biopsy), but it is very difficult to extract information from myriads of EV molecules. We propose a new technology for molecular profiling of single EVs to break the diagnostic and therapeutic gridlock in GBM.
Goal of project: We will harness EVs for liquid biopsy with a radically different technology. We bring together four disciplines (bioengineering, oncology, physics and tumour/EVs biology) to develop a new nanoplatform for molecular analysis of single EVs. This approach will yield a physical representation of molecular complexity of tumour cell populations, removing the roadblock in development of effective therapies.
Project description: Study on GBM will help us establish a broader link between physical and molecular properties of EVs. Our approach combines EV confinement in nanocavities, permitting simultaneous charge and size profiling, along with molecular profiling based on a method called Surface-Enhanced-Raman-Spectroscopy (SERS). This technology will output a physical fingerprint reflecting the bioactive cargo of a single glioma EV, including molecules responsible for malignancy and drug resistance.
Future impact: The ability to obtain a real-time glimpse into molecular hallmarks of cancer could transform the outcomes of presently incurable brain tumours such as GBM and metastatic cancers. This non-invasive liquid biopsy utilizing single EV physical properties and decoded SERS signal will enable treating each patient individually according to the unique molecular landscape of their specific cancer, moving away from the present ‘one-size-fits-all’ paradigm to more adaptive and effective protocols.