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

Overview

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 important 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 of immune, vascular or other microenvironmental components adds meaningful biological or pharmacological information.

The project is expected to generate patient-derived model workflows, standardised protocols and quality-control criteria that support the reliable use of these systems for functional studies. Selected models will also provide a platform for investigating therapeutic sensitivity and resistance across biologically diverse breast cancers.

Skills and experience

We are seeking a full-time, highly motivated PhD candidate interested in working at the interface of cancer biology, patient-derived models and advanced in vitro technologies.

This project would particularly suit a student with a background or strong interest in:

• biomedical science
• cancer biology
• cell and molecular biology
• biotechnology
• tissue engineering
• biomedical engineering
• a related discipline.

Previous experience in mammalian cell culture is highly desirable. Experience in one or more of the following would be beneficial:

• primary human tissue or organoid culture
• 3D cell culture
• breast cancer biology
• biomaterials or hydrogels
• microscopy and image analysis
• molecular biology or histology
• drug-response assays.

Applicants do not need to have experience across all these areas. A strong candidate with relevant biological experience and an interest in developing complementary skills in microphysiological systems and oncology NAMs would be encouraged to apply.

The ideal candidate will be curious, experimentally skilled and comfortable working with complex and biologically variable patient-derived material. They should be able to work independently while contributing effectively within a multidisciplinary academic and industry-linked team.

How to apply

Submit your application via email n.bock@qut.edu.au with the subject line 'PhD–MiPSET-PDBNAM–Your Surname'.

Your application must include:

• a cover letter by the applicant (maximum one page)
• an up-to-date CV indicating previous laboratory experience and skills, and the details of two referees (including their email addresses)
• your academic transcript.

Shortlisted applicants will be invited to an interview.

Scholarships

You may be eligible to apply for a research scholarship.

Explore our research scholarships

Keywords

• breast cancer
• patient-derived models
• organoids
• new approach methodologies (NAMs)
• microphysiological systems
• preclinical research
• tumour microenvironment
• therapy response
• extracellular matrix
• disease models
• preclinical models
• disease models
• 3D cell culture
• drug response

Contact

Contact the supervisor via email n.bock@qut.edu.au for more information with the subject 'PhD–MiPSET-PDBNAM–Your Surname'.