3D Screening of Compounds for Cancer Therapy

Reading time: 4 minutes

Sydney Scatigno

Over the last couple of decades, cancer research has made strides in improving the pre-clinical assessment of novel compounds. Compound screening, the process of assessing new compounds for efficacy, across various cell lines is an important step in finding the optimal drug candidate downstream in the drug development process. 3D in vitro screening is an effective technology to accomplish this goal. Here, I will examine the various components required to screen drugs using 3D in vitro techniques. 

There are 3 components to the screening technique. The first component is the cell source. The cells used are important to the integrity of the study, as they determine how well the results will be interpreted and how predictive the results will be in-vivo (in the human body). One useful type of cells are immortalized cell lines. These are lines that have been well characterized and are reliably cultured leading to consistent results. Induced pluripotent stem cells (iPSCs) and adult stem cells are another useful cell type. The advantages include the ability to differentiate them into different cell types, allow for the patients’ genetic background to be expressed and are also widely available. Patient-derived-xenografts (PDX) can also be used for cell screening, these are cancer cell lines developed directly from patient tumors. The availability of PDX lines and the wide range of tumor types available make these excellent cells¹.

The next component is tissue type. Assays can be performed using live cells, using the cells to grow tumors and acquire the tissue material or implanting cells into a matrix. The various tissue types are spheroids, organoids, precision cut slices and extracellular matrix. Tumor spheroids are masses of cells from one of the sources described above that have the same architecture as cancer cells and are embedded within a 3D matrix¹. 3D matrices are commonly formed using agarose gel that the spheroids are embedded into². The spheroids are both scalable and can integrate multiple cell types. Organoids can self-organize in 3D and are built from stem cells. This tissue type is available commercially and can be derived from healthy and diseased cells. The main difference between these two tissue types is that the spheroids can be formed using various cell types whereas organoids are specifically derived from stem cells and can be engineered to form specific organ types³. Precision cut slices are tumors that have been stained and sliced to be used for ex-vivo (performed outside of a living body) experiments. These slices are useful because they have intact tumor composition as well as the tumor blood supply, or vasculature. The extracellular matrix is made from synthetic polymer networks to mimic the body’s natural environment and are useful because you can have more control over the cellular growth and migration. This control is important to the screening process because it allows for limited variability and more reliable data¹. 

Finally, the various technologies that are seen are bioprinting, bioreactors, and organs-on-a-chip. Bioprinting is similar to 3D printing but instead prints with cells or other biological materials and can be used to imitate tissues. One of the benefits of this technique is that these printed tissues can be uniform and the tissue architecture can be controlled. Bioreactors can be used to expand cells in large quantities and while they can sometimes be more useful outside of oncology research, in areas such as cell therapy and manufacturing and genome sequencing, it is highly reproducible. Organ-on-a-chip systems are microenvironments which allow tissue to grow and the microfluid environment can mimic metastasis. They also can allow for immune cells to flow through¹. You can read more about organ-on-a-chip systems here³.

Combining these components leads to the large-scale evaluation of drug candidates across a wide range of cell types in a cost-effective way. As the technology advances 3D screening can also be used for disease progression modeling. 

Edited by Kate Secombe

1. Scheuler,Julia A.. (2022) ‘How to build a tumor: An industry perspective’, Drug Discovery Today, Vol 27 (10).
2. Li, Nancy T. (2020) ‘Chapter 19 – Tissue-engineered 3D cancer microenvironment for screening therapeutics’, Science Direct, 453-479. Available at: https://www.sciencedirect.com/science/article/pii/B9780128181287000198 (Accessed: 11/17/2022).
3. Barbuzano, J. (2017) Organoids: A new window into disease, development and discovery. Available at: https://hsci.harvard.edu/organoids#:~:text=Organoids%20are%20tiny%2C%20self%2Dorganized,only%20certain%20types%20of%20cells. (Accessed: 11/17/2022)

Image credits: https://upload.wikimedia.org/wikipedia/commons/a/a0/96_well_plate.jpg