Progress and perspective of organoid technology in breast cancer research

Abstract

Breast cancer, a malignant tumor with a high incidence in women, lacks in vitro research models that can represent the biological functions of breast tumors in vivo . As a new biological tool, the organoid model has unique advantages over traditional methods, such as cell culture and patient-derived xenografts. Combining organoids with other emerging technologies, such as gene engineering and microfluidic chip technology, provides an effective method to compensate for the deficiencies in organoid models of breast cancer in vivo . The emergence of breast cancer organoids has provided new tools and research directions in precision medicine, and drug research. In this review, we summarized the merits and demerits of organoids compared to traditional biological models, explored the latest developments in the combination of new technologies and organoid models, and discussed the construction methods and application prospects of different breast cancer organoid models.

Keywords: Bioengineering; Breast cancer; Organoids; Preclinical model.

Figure 1

Construction of the four biological models. The schemes show four ways to construct biological models. (A) 2D cell culture model uses scissors or other tools to separate tissues, add tissues into digestive juices to get single cells, and then transplant the single cells into the appropriate culture medium to get a monolayer cell structure. (B) PDX model isolates and amplifies tumor cells, and then the tumor cells are transplanted into immunodeficient mice, and the mice are cultured to produce tumor mice. (C) Organotypic tissue slice culture is to obtain the appropriate size of organ tissues, freeze or paraffin-wrap tissues, use the microtome to get tissue sections, and put them into a culture medium. (D) Organoid model uses the self-organizing function of somatic stem cells or human-induced stem cells, adding specific growth factors to induce and differentiate into organoids. 2D: Two-dimensional; PDX: Patient-derived xenograft.

Figure 2

Evolution of organoids. The timeline of organoid culture development. Key milestones and breakthroughs of organoid technologies. Organoid technology began in 2009. Cleve's team of Hubrecht Institute in the Netherlands successfully cultured adult stem cells into crypts and villi structures of the small intestine, which is a milestone in the development of organoids. ESCs: Embryonic stem cells; iPSCs: Induced pluripotent stem cells; PSCs: Pluripotent stem cells.

Figure 3

Application of the breast organoid model. The diagram summarizes the combination and application of breast organoids and emerging technologies, including the combination of genetic engineering and microfluidic chip technology and their applications in the biological sample library, drug testing, and precision medicine.

Figure 4

Construction of an organoid chip. The schematic diagram shows an idea of organoid-chip construction. Human iPSCs are cultured into corresponding breast organoids and other organoids (such as immune organs) through organoid-chip technology, and the combination of them through organoid-chip technology can not only help researchers to observe the changes of organoids by controlling the organ microenvironment and external stimuli, but also help them to observe the interactions between different organs. iPSC: Induced pluripotent stem cells.