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

Vision: 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. We invite you to assess our application and support our efforts to advance this critical field.