The discovery of new drugs, including oncology drugs, starts with drug screening. Chemical screens are studies that are traditionally large-scale endeavors carried out by big pharmaceutical companies such as Roche, Merck, Johnson & Johnson, Eli Lily, and GSK, just to name a few. However, in the past decade, academic screening centers have been established, as well as many joint-ventures between pharmaceutical companies and academic institutions.
Traditionally, drug screening campaigns are conducted in two-dimensional (2-D) microtiter cell culture plates. In 2-D cell culture model systems, primary or immortalized cells are seeded in cell culture plates or dishes, which are chemically treated to help cells adhere and proliferate. While it is true that 2-D cell culture systems are easy to use and economical, the major disadvantage of 2D screening is that cells grow as monolayers, which is not at all how cells grow in vivo.
Recently, three-dimensional (3-D) cell culture systems have become an increasingly popular choice for drug screening. Despite the high cost and certain challenges in cell handling, 3-D systems closely mimic the cells in vivo:
- Cells in 3-D grow as multilayered spheres with enriched cell-cell contact. In contrast to 2-D culture (Fig. 7, left), Glioblastoma multiforme (GBM) cells grown in 3-D (Fig. 7, right) closely mimic GBM tumor spheres in vivo.
- Cells in 3-D display very different response patterns to drug treatment. Cells tend to respond at higher levels of sensitivity to drug treatment in 2-D but tend to show reduced sensitivity in 3-D. Needless to say, this observation is of crucial clinical significance.
