The Variety of 3D Breast Cancer Models for the Study of Tumor Physiology and Drug Screening

Abstract

Breast cancer is the most common cancer in women and responsible for multiple deaths worldwide. 3D cancer models enable a better representation of tumor physiology than the conventional 2D cultures. This review summarizes the important components of physiologically relevant 3D models and describes the spectrum of 3D breast cancer models, e.g., spheroids, organoids, breast cancer on a chip and bioprinted tissues. The generation of spheroids is relatively standardized and easy to perform. Microfluidic systems allow control over the environment and the inclusion of sensors and can be combined with spheroids or bioprinted models. The strength of bioprinting relies on the spatial control of the cells and the modulation of the extracellular matrix. Except for the predominant use of breast cancer cell lines, the models differ in stromal cell composition, matrices and fluid flow. Organoids are most appropriate for personalized treatment, but all technologies can mimic most aspects of breast cancer physiology. Fetal bovine serum as a culture supplement and Matrigel as a scaffold limit the reproducibility and standardization of the listed 3D models. The integration of adipocytes is needed because they possess an important role in breast cancer.

Adipose Tissue in Breast Cancer Microphysiological Models to Capture Human Diversity in Preclinical Models

“…More importantly, data have evidenced increases in breast cancer incidence to 16.9 per 100,000 women, while efforts in drug development lead to limited efficacy. Approximately 85% of the drugs in early clinical trials fail due to poor clinical efficacy, toxicity, and drug-like properties [ 2 , 3 ]. These roadblocks to clinical translation have initiated a shift in the reexamination of preclinical models used for breast cancer drug development.…”

“…Instead of relying on the addition of foreign ECM, this model relies on the direct generation of ECM from the cells themselves. Spheroids have already achieved success in breast cancer research as biomimetic in vitro models to study underlying mechanisms in tumor biology ( Table 1 ) [ 2 , 21 , 62 , 70 , 71 , 72 , 73 , 74 , 75 ]. Although the exclusion of stromal cell populations such as adipocytes or ASCs in spheroid models is a current shortcoming, progress has been made in this model, as demonstrated by the promising results from several studies [ 49 , 62 , 64 , 65 , 66 ].…”

“…They can also incorporate both two-dimensional and three-dimensional formats in which cells are either cultured directly on devices or fully encapsulated into the desired ECM [ 35 ]. For example, select models have evaluated the efficacy of doxorubicin delivery into breast tumor spheroids by mimicking vascular flow, malignant epithelial cell invasion into healthy stroma, and breast ductal carcinoma in situ (DCIS) progression to invasive ductal carcinoma (IDC) [ 2 , 78 , 79 , 80 ]. Despite advancements in organ-on-a-chip technology, few studies have demonstrated the utility of examining adipose-breast cancer interactions in a comprehensive manner.…”

“…However, with advancements in 3D bioprinting (3DBP) technology, more customizable, comprehensive models have been developed, including systems mimicking vascular-like tubes, artificial skin, lung, kidney, cartilage, and brain [ 35 ]. Bioprinted models simulating breast, brain, ovarian, and skin cancers have been optimized over the past five years [ 2 , 81 , 82 , 83 , 84 , 85 ]. Bioprinting can be described as a process that deposits materials by layering to generate a three-dimensional structure.…”

Paper-Based Coculture Platform to Evaluate the Effects of Fibroblasts on Estrogen Signaling in ER+ Breast Cancers

“…Stromal fibroblasts and adipocytes have been incorporated into three-dimensional (3D) culture formats, including mammosphere cultures, microfluidic devices, and bioprinted constructs. − Each of these setups has positive and negative aspects. Mammospheres are easily set up but are limited to microscopy or histology readouts as the different cell types are in contact.…”