TEP-eDx: Validating the use of Tumour Educated Platelets for early cancer diagnosis

Earlier detection greatly improves outcomes for patients with cancer, and studying the gene changes in cancer cells greatly helps in identifying risks and 'tailoring' treatment.

There is currently significant interest in ‘liquid biopsy’ approaches that are geared towards enabling cancer detection via blood sampling rather than tissue biopsy.

However, as current approaches are generally technically challenging and of poor sensitivity, novel approaches that would improve detection would be highly beneficial.

Platelets are highly abundant blood cells that take up proteins and molecules that they encounter while circulating in our blood.

Sampling platelets from a simple blood test may thereby provide a 'window' to detect and study proteins released by cancer cells.

In this proposal, we aim to validate “tumour educated” platelets (TEPs) as an enticing platform for early cancer diagnosis.

This will be achieved via three experimental objectives: (1) determining if enriching for DNA fragments associated with platelets may be more sensitive than current ‘liquid biopsy’ techniques for cancer detection; and if there are specific fragmentation and epigenetic ‘signatures’ identifiable in patients with cancers; (2) determining the role and consequence of tumour cell-derived extracellular vesicles in transferring tumour cell protein biomarkers to platelets; (3) identifying if biomechanical properties are present that are unique to platelets exposed to tumour cells.

Our overarching goal is to validate and develop TEPs as a new platform for non-invasive cancer diagnosis and molecular profiling that may be applicable to a range of different types of cancers.

This project will cement new collaborations formed between clinicians, scientists and physicists to undertake highly innovative experiments.

This project will leverage significant combined expertise and maximising utilization of key resource facilities at each host institute.

This includes expertise in platelet biology/cancer genomics and clinical expertise (Psaila, Oxford), computational biology and novel analytical pipelines (Thongjuea, Oxford), extracellular vesicles and cancer cell biology (Gregory, Edinburgh), advanced imaging (Meissner, Swansea) and instrumentation development (Gersen, Bristol), with additional collaborators at each institute, thereby delivering significantly more impact than would be possible from a single institution project.

This proposal is the natural extension of a CRUK Innovation Award (2019), closely aligns with the key focus areas of the CRUK Early Detection Programme and has a clear line of sight to clinical translation.