Engineering prostate cancer in vitro: what does it take?

A key challenge in the clinical management and cause of treatment failure of prostate cancer (PCa) is its molecular, cellular and clinical heterogeneity. Modelling systems that fully recapitulate clinical diversity and resistant phenotypes are urgently required for the development of successful personalised PCa therapies. The advent of the three-dimensional (3D) organoid model has revolutionised preclinical cancer research through reflecting heterogeneity and offering genomic and environmental manipulation that has opened up unparalleled opportunities for applications in disease modelling, high-throughput drug screening and precision medicine. Despite these remarkable achievements of organoid technology, several shortcomings in emulating the complex tumor microenvironment and dynamic process of metastasis as well as the epigenome profile limit organoids achieving true in vivo functionality. Technological advances in tissue engineering have enabled the development of innovative tools to facilitate the design of improved 3D cancer models. In this review, we highlight the current in vitro 3D PCa models with a special focus on organoids and discuss engineering approaches to create more physiologically relevant PCa organoid models and maximise their translational relevance that ultimately will help to realise the transformational power of precision medicine.