Tumour avatars of patients for assessment of therapeutic efficacy

Primary Supervisor: Professor Eric O'Neill

Project Overview

Advances in therapeutic development and clinical translation are hindered by a lack of representative human preclinical models. As a consequence, the pharmaceutical industry is beset with costly failures at advanced stages of development due to lack of efficacy, unpredicted adverse events or inappropriate patient selection. It is well recognised that better human models would massively strengthen drug development pathways and accelerate clinical development of lead compounds. Patient-derived tumour slices provide a platform through which tumour, stroma and immune infiltrate can be studied in their native architecture. Furthermore, personalised healthcare is undoubtedly the future of the medical care industry. Providing precise, tailored treatment plans based on for an individual’s unique medical statistics will not just revolutionise medical journeys, but will also reduce costs for health providers. However, current personalised care approaches suffer from the representation problem. Thus, there is a need to have representative human models and patient avatars that can faithfully predict therapeutic responses for each patient.

Our technology is the first to achieve therapeutic and immunological monitoring of patient tumours in real-time that can faithfully report on a patients clinical journey (Hughes et al. Science Adv 2024).

Through this system, therapeutics can be investigated for their impact throughout the tumour and normal tissue allowing analysis of benefit, toxicity and intra-patient variation.  This can accelerate therapeutic development and advance the potential of immunotherapy through robust pre-clinical human models. 

This project involves the further development of this technology to improve the engineering of the avatar apparatus as a medical device, determining the ability to employ non-labelled imaging of tumour avatars and elucidation of higher order tumour organisation into cell modules to determine therapeutic responses. Additional project may centre on the development of the avatar platform to assess cell based therapies for pancreatic and oesophageal cancer.

Training Opportunities

The student will acquire skills in tissue and cell culture and will be trained in all aspects of:

• Molecular and metabolic profiling of cells and tissues
• Bioinformatics and biostatistics related to the project

References:

Hughes, D., Evans, A., Go, S., Eyres, M., Pan, L., Mukherjee, S., Soonawalla, Z., Willenbrock, F. and O’Neill, E., 2024. Development of human pancreatic cancer avatars as a model for dynamic immune landscape profiling and personalized therapy. Science Advances, 10(27), p.eadm9071.