Abstract WS2-1: Genome editing in human organoids as new models for discovery

Abstract

Abstract Use of human organoids as new models for discovery. Despite significant advances, there are circumstances where mouse models remain inadequate to model cancer. Human organoid cultures are becoming established as a useful adjunct to mouse models because they enable the propagation of both normal and cancerous tissues in the lab for functional studies, disease modeling, and drug screening. Organoids can be generated from induced pluripotent stem cells or directly from donor tissue samples (e.g. normal breast tissue or tumors). In the latter approach, breast organoid cultures are grown in a hydrogel that mimics the basement membrane and are bathed in a cocktail of growth factors, vitamins, and compounds that mimic the microenvironment provided by stroma, resulting in the growth of cells in a polarized fashion to recapitulate breast acinar- and duct-like structures. Breast epithelial cells within organoids are able to differentiate into all of the major mammary epithelial lineages, and hence organoids can be used to study several types of epithelial lineages and their relative contributions to tumor development. In addition, breast cancer organoids can be used to expand heterogeneous populations of tumor cells for in vitro assays. For example, genome editing approaches can be used to model mutations associated with breast cancer, and compound screening approaches can facilitate target discovery. In this educational talk, we will review some of these recent advances, consider advantages and disadvantages of this model system, and discuss some practical considerations for bio-banking efforts and downstream applications. Citation Format: JM Rosenbluth. Genome editing in human organoids as new models for discovery [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr WS2-1.