Engineering Prostate Cancer from Induced Pluripotent Stem Cells—New Opportunities to Develop Preclinical Tools in Prostate and Prostate Cancer Studies

Abstract

One of the key issues hampering the development of effective treatments for prostate cancer is the lack of suitable, tractable, and patient-specific in vitro models that accurately recapitulate this disease. In this review, we address the challenges of using primary cultures and patient-derived xenografts to study prostate cancer. We describe emerging approaches using primary prostate epithelial cells and prostate organoids and their genetic manipulation for disease modelling. Furthermore, the use of human prostate-derived induced pluripotent stem cells (iPSCs) is highlighted as a promising complimentary approach. Finally, we discuss the manipulation of iPSCs to generate ‘avatars’ for drug disease testing. Specifically, we describe how a conceptual advance through the creation of living biobanks of “genetically engineered cancers” that contain patient-specific driver mutations hold promise for personalised medicine.

Patient-Derived Xenograft vs. Organoids: A Preliminary Analysis of Cancer Research Output, Funding and Human Health Impact in 2014–2019

“…PDO are valuable tools for cancer research and pre-clinical testing and their use could be further enhanced to facilitate drug screening [ 44 ]. Combining PDO systems with, for example, induced pluripotent stem cells, which can overcome some of the issues associated with primary cell culture, or with other human 3D culture platforms that incorporate dynamic culture conditions could offer more flexibility for evaluating tumor development, drug delivery and potential molecular targets [ 45 ].…”

Functional Drug Screening in the Era of Precision Medicine

“…iPSCs are somatic cells reprogrammed by four transcription factors such that they can differentiate into multiple cell lineages and organoid culturing of iPSCs mimics tumorigenesis and have been established for multiple organs. iPSCs provide a more reliable source of cells compared to traditional 2D culture and could overcome issues with genetic drift that occur in long term primary culture ( 79 ). Despite the potential utility of the iPSC model, this reprogramming, like CR, can result in loss of the drug resistance, metastatic potential, and tumorigenic behaviors of the original cells; likewise, the epigenetic reprogramming implicated in this process may alter the expression of oncogenes and affect several cancer-related pathways ( 79 ).…”

iPSC-Derived Organoids as Therapeutic Models in Regenerative Medicine and Oncology

“…This study allowed to determine the early genomic changes occurring in the AT2 cells some of which were similar to transcriptomic features of in primary lung adenocarcinoma such as overexpression of Sox9 ( 38 ). Thus, iPSC-derived cancer organoid technology is expected to expand during the next decade, with several models developed for other cancers ( 39 , 40 ) with increasing implication of microfluidic technology to study drug sensitivity ( 41 ). These technologies will also benefit from the molecular analyses and bioinformatics techniques with discovery of novel targets leading to therapeutic intervention ( 34 , 42 ).…”