Title: Exosomal lipidome as diagnostic proxy for early detection and phenotyping of solid tumours
Funder: Cancer Research UK

Abstract: Exosomes are found in high concentrations in body fluids of cancer patients and participate actively in the modulation of the cellular microenvironment facilitating tumorigenesis, cancer migration and establishment of metastatic niches. Cancer exosomes have significant potential as body fluid-based cancer biomarkers for early detection of cancer and tumour recurrence. Our recent results have successfully demonstrated that tumour cell-derived exosomes carry a lipid profile sufficiently specific for the identification of their progenitor cells. Also, significant differences have been found between the lipid profile of exosomes released by healthy and tumour cells. As such, the current proposal will focus on the development and validation of a methodology to isolate and characterise exosomes including the development of single exosome mass spectrometry. The latter technique will allow the characterisation of large exosome populations and detection of the diagnostically relevant sub-populations in the blood samples of patients. We will use breast cancer cell lines and blood samples obtained from breast cancer patients to demonstrate feasibility, however the real targets for these diagnostic methods will be pancreatic and ovarian cancer where early detection is a serious unmet need. This research programme will contribute to the understanding of exosome metabolism and its role in tumourgenesis, by applying single-exosome analysis techniques. The identification of potential body fluid-based lipid biomarkers will have a great impact in the early detection of cancer, with potential future applications in a routine clinical environment, and therefore, increase in patient survival rates.

Lay abstract: Exosomes are found in high concentrations in body fluids of cancer patients and participate actively in the modulation of the cellular microenvironment facilitating tumorigenesis, cancer migration and establishment of metastatic niches. Cancer exosomes have significant potential as body fluid-based cancer biomarkers for early detection of cancer and tumour recurrence. Our recent results have successfully demonstrated that tumour cell-derived exosomes carry a lipid profile sufficiently specific for the identification of their progenitor cells. Also, significant differences have been found between the lipid profile of exosomes released by healthy and tumour cells. As such, the current proposal will focus on the development and validation of a methodology to isolate and characterise exosomes including the development of single exosome mass spectrometry. The latter technique will allow the characterisation of large exosome populations and detection of the diagnostically relevant sub-populations in the blood samples of patients. We will use breast cancer cell lines and blood samples obtained from breast cancer patients to demonstrate feasibility, however the real targets for these diagnostic methods will be pancreatic and ovarian cancer where early detection is a serious unmet need. This research programme will contribute to the understanding of exosome metabolism and its role in tumourgenesis, by applying single-exosome analysis techniques. The identification of potential body fluid-based lipid biomarkers will have a great impact in the early detection of cancer, with potential future applications in a routine clinical environment, and therefore, increase in patient survival rates.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS