Techniques for culturing functional human breast epithelium in three-dimensional (3D) matrices have been championed for more than 30 years by Mina Bissell. Additionally, around a decade ago, Sasai and colleagues pioneered pluripotent stem cell (PSC)–based technology to create organoids that mirror specific parts of the central nervous system (CNS). Lancaster and Knoblich modified this technology and provided particularly notable examples of “mini-brain” structures. While PSCs can be used to model everything ranging from tissues to organismal development, adult stem cells (ASCs) can also be isolated to generate organoid models of the primary tissues in which they reside. Specific growth factor cocktails allow long-term expansion of ASC organoids by mimicking the organ stem cell niche, as first established for mouse and human intestine and airway epithelium. The organoid structures generated from PSCs and ASCs reflect crucial tissue features in terms of overall architecture, the collection of differentiated cell types, and tissue-specific function. Organoids thus represent a model system that can be compared to traditional genetically engineered mouse models (GEMMs), cell lines, and patient-derived xenografts (PDXs).

As a definition, organoids are microscopic self-organizing, three-dimensional structures that are grown from stem cells in vitro. They recapitulate many structural and functional aspects of their in vivo counterpart organs. This versatile technology has led to the development of many novel human cancer models. It is now possible to create indefinitely expanding organoids starting from tumor tissue of individuals suffering from a range of carcinomas. Alternatively, CRISPR-based gene modification allows the engineering of organoid models of cancer through the introduction of any combination of cancer gene alterations to normal organoids. When combined with immune cells and fibroblasts, tumor organoids become models for the cancer microenvironment enabling immune-oncology applications. Emerging evidence indicates that organoids can be used to accurately predict drug responses in a personalized treatment setting. I will illustrate the current state and future prospects of the rapidly evolving tumor organoid field through examples from my lab.