Billions of dollars are invested globally into the clinical approval of new drug compounds, but only a small handful of new chemical entities are approved by the Food and Drug Administration (FDA) each year. Cell-based assays have been a key component in streamlining the drug development process, helping drugs be brought to the market in a quick and efficient manner, and their technological evolution is not slowing down.
While cytotoxicity remains a primary effect that drug developers use cell based assays to quantify, biological activity, biochemical mechanisms and off-target interactions are also being investigated using this technique. Due to their amenability to miniaturization and multiplexing, cell cultures are being used for high-throughput screening (HTS) to test many compounds under different conditions in parallel.
Going Beyond Cytotoxicity
Technological developments in physiology and molecular biology are allowing cull culture scientists to investigate the effects of drug compounds on multiple cell phenotypes. For example, protein complementation assays reveal the effects of such compounds on protein-protein interactions, which often stimulate signaling cascades in cellular pathways. As a result, signaling pathways such as those involved in the proliferation of cancer can be further investigated.
Calcium signaling is another highly informative readout of the effects of a given drug compound on cellular functions, since calcium signaling is involved in many important physiological processes. New molecular biology tools are allowing researchers to monitor calcium signaling using cell-based assays, which could have significant implications to the drug discovery market.
With the wealth of functional genomics data available to us today, there are many genes to choose from to investigate the effects of a drug on various cellular processes. Reporter gene technology allows researchers to do just this in cell cultures, and as with the other tools, automated fluorescence microscopy and image analysis allow integration into an automated HTS pipeline to streamline the path to effective discovery.
The Next Dimension of Cell-based Assays
Three-dimensional cell cultures used to be thought of as expensive and cumbersome, but technological developments have changed this. Spheroids show gene expression profiles that are closer to clinical profiles than traditional 2D cell cultures. Furthermore, they better mimic tumors, since they have a hypoxic core and experience a nutrient gradient throughout their mass. Researchers in Germany and the USA have published a protocol for growing 3D cultures of numerous commonly used cancer cells lines so that drug screening can be performed on these.
Modern cell-based assays are combining the advantages of animal models and cell cultures to allow drug developers to identify problems with drug candidate leads at early stages. As a result, effective and safe drugs can be brought to those that need them, quicker.
Want to learn more about cell-based assays and taking your cells to the edge? Watch our on-demand webinar in the Cell Culture Cafe: Take your cell-based assays to the edge.