Research Project

Personalised Medicine

Microfluidic system to grow colorectal organoids for use in stratified medicine

Current targeted treatments for cancer often fail because they are based on the identification of driver gene mutations or the expression of cancer pathway components which accurately predict drug responses in only a small subset of tumours. In reality, tumour development is a highly dynamic process leading to a vast intra- and inter-tumour heterogeneity that hinders accurate diagnosis, identification of effective treatment methods and contributes to therapeutic resistance. There is a need to identify improved, targeted drug therapies, to tailor treatments to patient-specific cancer subtypes and to minimise toxic side-effects.

Patient-derived organoids, 3D cell structures with organ-like characteristics grown from stem cells, have the potential to fulfil the unmet need for targeted therapies. Recent evidence has shown that drug- treated organoids mirror patient responses much more accurately than 2D in vitro and can be used as a powerful tool for efficacy and toxicity tests in drug discovery and genetics research. Morphologically and functionally, cancer organoids recapitulate many features of the tumours from which they were derived. Importantly, as living dynamic 3D systems they simultaneously integrate the output of each patient’s unique genetics, suggesting they may perform dramatically better at predicting therapeutic responses. Using such organoids in a personalised medicine approach, where organoids are generated from the patient’s own tissue, would allow the testing and determination of which available treatment method is most beneficial for the individual patient.

This project proposes a radical new approach using the patients’ own cancer cells to test available anti- cancer agents to identify the most efficient treatment option for each individual. The direct testing of drugs using patient-derived organoids presents a major technical challenge since organoids need to be expanded at scale from limited numbers of cells in patient biopsies from thousands of patients. The work proposed here will underpin an innovative solution to address this challenge through the miniaturisation and automation of a scaled-down organoid bioprocess.

In this project, the aim is to take a substantial step towards this ambitious goal by addressing the challenge of developing an effective microfluidic system to allow the growth, monitoring and treatment of small numbers of, difficult-to-handle 3D organoids. This aim will be facilitated by a cross disciplinary collaboration combining the engineering and commercial expertise of Cellesce, with the biological expertise of Professor Trevor Dale, and Dr Valle-Encinas at Cardiff University (CU) and the microfluidics know-how from Dr Damien King and the cell handling group at the Fraunhofer Project Centre for Embedded Bioanalytical Systems at Dublin City University ([email protected]), together with support from the Clinical Innovation Accelerator (CIA).

Funded by: Accelerate