Preclinical models advancing new therapies for prostate cancer

Patient derived xenografts (PDXs) are proving to be a huge game-changer in fast-tracking new and emerging therapies for prostate cancer patients. As part of a clinical-laboratory collaboration, Professor Mark Frydenberg AM (pictured below, left) has been working with Professor Gail Risbridger and Associate Professor Renea Taylor to develop state-of-the-art prostate cancer PDXs, known as the Melbourne Urological Research Alliance (MURAL) collection.

PDXs are reliable and representative preclinical models of cancer, where the tissue or cells from a patient’s tumour are implanted into immunodeficient or humanised mice. As a whole animal model rather than isolated tissue, PDXs have many benefits, most notably being the cancer cells are in a mixed ‘natural’ environment. This means they are not isolated as tumour cells and they interact with other cell types including immune cells and vascular cells, like a tumour would in a patient, providing a very close representation of the disease.

A bank of 59 well-characterised prostate cancer PDXs, derived from 41 tumours from 30 patients and supported by associated resources (organoids, serum, DNA/RNA profiles and tissue), is available for collaborative projects. The collection includes many standout characteristics that will help accelerate discoveries including representing the clinico-pathological and genomic spectrum of prostate cancer, from treatment-naïve primary tumours to castration-resistant metastases, the availability of matched primary and metastatic tumours from the same patient, and different metastatic sites from the same patient.

The MURAL collection has been an eagerly anticipated research resource that will facilitate pre-clinical testing of new and emerging targeted therapies and biological discovery in prostate cancer. Taking eight years to create, and published in the esteemed international journal Nature Communications, it is now garnering both national and international attention and will drive significant research discoveries in the future.

Communications. 12(1):5049. doi: 10.1038/s41467-021-25175-5.