Patient-derived oncology NAMs for preclinical breast cancer research and therapeutic evaluation

We're looking for students to study this topic.

New approach methodologies (NAMs), including advanced 3D cultures and microphysiological systems (MPS), are creating new opportunities to develop more human-relevant approaches for preclinical cancer research. However, translating these technologies from established cell lines to patient-derived tumours remains challenging because of limited tissue availability, tumour heterogeneity and variability in model establishment and performance.

Building on established QUT expertise in patient-derived bioengineered breast tumour models, this project will develop robust and reproducible patient-derived oncology NAMs for preclinical breast cancer research and therapeutic evaluation.

Breast cancer provides an significant application because it encompasses multiple molecular subtypes, treatment responses and disease sites. The student will investigate how patient-derived breast cancer cells and organoids can be reproducibly established within defined three-dimensional extracellular matrix environments while retaining biologically and therapeutically relevant tumour characteristics.

Models may be generated from fresh primary and metastatic breast cancer tissues and established patient-derived resources, including patient-derived xenograft (PDX)-derived material. The project will investigate how tumour origin, extracellular matrix properties and increasing cellular complexity influence model performance and therapeutic response.

Selected models will be used for functional evaluation of standard‑of‑care, clinically relevant and/or genomically nominated therapies. More complex models may subsequently incorporate immune, vascular,



stromal or other relevant microenvironmental components to determine whether these features alter tumour phenotype, therapeutic sensitivity or resistance.

A key focus will be to establish models and workflows that are reproducible, transferable and suitable for broader application as preclinical oncology NAMs. The precise tumour models, matrix conditions, therapeutic questions and cellular combinations will be refined with the successful student, providing substantial scope for them to contribute ideas and shape the direction of the PhD.

Research activities

This project forms part of the ARC Training Centre for Microphysiological System Technology ( MiPSET ), a national industry‑linked initiative developing advanced MPS and other human‑relevant NAM technologies for biomedical research and medical product development.

The student may contribute to activities including:

- establishing and optimising patient‑derived breast cancer organoid and 3D tumour models
- working with fresh primary and metastatic breast cancer tissues and PDX‑derived tumour material
- comparing model establishment and behaviour across breast cancer subtypes and disease sites
- evaluating defined and tuneable extracellular matrix environments for patient‑derived tumour culture
- determining how matrix composition and properties influence tumour viability,



phenotype and therapeutic response
- developing robust and tissue‑efficient workflows for generating NAMs from limited patient samples
- functionally evaluating standard‑of‑care, clinically relevant and genomically nominated therapies
- comparing therapeutic responses across patient‑derived models and microenvironmental conditions
- identifying models displaying differential therapeutic sensitivity or resistance
- incorporating immune, vascular, stromal or other relevant cellular components into selected models
- determining whether increasing biological complexity alters tumour behaviour or response to therapy
- applying imaging, histological, molecular and functional readouts to characterise model performance
- establishing reproducible protocols, quality‑control criteria and response metrics
- evaluating the reproducibility and transferability of model‑generation and therapeutic‑evaluation workflows between academic and industry laboratories.

The successful candidate will work within a multidisciplinary environment spanning cancer biology, tissue engineering, biomaterials and microphysiological systems. The project will also leverage the expertise of MiPSET industry partners AimingMed and Gelomics in organoid culture media and advanced hydrogel‑based 3D culture systems.

Outcomes

This project aims to establish robust, reproducible and transferable patient‑derived oncology NAMs for preclinical breast cancer research and therapeutic evaluation.

The research will determine how tumour origin and extracellular matrix context influence model establishment, biological fidelity and therapeutic response, and whether the incorporation

📌 Associate Professor Nathalie Bock (Australia)
🏢 Queensland University Of Technology
📍 Australia