Using a defined 3D human organoid model to replace the use of animals in the screening and evaluation of treatments for prostate cancer

Prostate cancer (PCa) is the second most common cancer amongst men worldwide and a leading cause of cancer-related deaths. Despite advances in treatment, resistance to therapies like androgen deprivation therapy (ADT) remains a significant challenge. Our project aims to develop and validate a cutting-edge, xeno-free iPSC-derived prostate organoid model to screen and evaluate PCa treatments, ultimately reducing and replacing animal use in research.

Objectives:

Validation: Demonstrate the suitability of our in vitro organoid model for screening and evaluating PCa treatments, reducing reliance on animal models.
Alternative Approaches: Explore alternative treatments and assess drug combinations to sensitise organoids to therapy.
Ethical Considerations: Integrate the 3Rs (Replacement, Reduction, Refinement) principles into the training of our PhD candidate studying cancer biology.

Areas of Focus:

Organoid Model Development: Utilise genetically engineered iPSCs to create prostate organoids that mimic the structural complexity of in vivo prostate tissue.
Drug Screening: Perform high-throughput screening of FDA-approved drugs targeting key pathways in PCa cell lines, organoids and PCa tissues.

ADT Resistance: Develop ADT-resistant organoids to investigate drug responses in a more complex model.
Nanoparticle Drug Delivery: Collaborate with experts to enhance drug delivery using nanoparticles targeting cancer cells.
Importance: Prostate cancer research lacks models that accurately represent the disease’s complexity, particularly the transition from hormone-sensitive to hormone-resistant states. Our innovative iPSC-derived organoid model addresses this gap, providing a valuable tool for preclinical drug testing. This model is free of any animal-derived components and reduces the use of animal models, aligning with ethical research practices.

Why It Will Succeed:

Innovative Approach: Our model faithfully replicates prostate tissue histology and allows reconstruction of patients’ genotypes.
Collaborative Effort: We are working with leading experts and institutions to ensure the success and adoption of our model.
Ethical Commitment: By integrating the 3Rs principles, we are committed to ethical and responsible research practices.
Global Impact: This model benefits researchers studying PCa, benign prostatic hyperplasia (BPH), and urinary tract development, making it relevant to a large international scientific community.
 

Our project aims to revolutionise prostate cancer research by providing a reliable, ethical, and innovative model for drug screening and evaluation.