Engineering prostate cancer in vitro: what does it take?

Abstract

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.

Fig. 1. Properties of 3D prostate cancer model systems.

Overview of advantages and limitations of each 3D model for studying prostate cancer (Created with BioRender.com).

Fig. 2. Engineering strategies to enhance the 3D prostate cancer organoid model for precision medicine.

A summary outlining the cell sources and bioengineering tools and approaches that may facilitate development of a 3D prostate cancer organoid model that fully recapitulates the tumor microenvironment and overcomes limitations of the current preclinical systems. Such an engineered cancer model would allow more translationally relevant mechanistic studies, high-throughput drug screening, assessment of immunotherapies, generation of biobanks and recreation of the metastatic process and sites for the development of personalised medicines. (Created with BioRender.com).

Fig. 3. Recommendations for the future of prostate cancer research.

A co-culture system integrating 3D engineered organoids and an organ-on-chip platform to incorporate the multiple cell types of the TME would allow development of a more physiologically relevant PCa model amenable for clinical translation and precision medicine. (Created with BioRender.com).