By binding to target proteins, most drugs are able to interrupt unwanted or facilitate desired biochemical reactions. While it’s difficult enough to identify the target protein and then discover a molecule that will do the right thing, an extra challenge that researchers face is the inability to monitor whether the drug actually binds to the proteins within the living cells of a tissue sample.
Now researchers from the Karolinska Institutet, a medical university in Stockholm, Sweden, are reporting in the journal Science the development of a breakthrough technology called CETSA (Cellular Thermal Shift Assay) that allows for just that. Daniel Martinez Molina, a leader of a project to bring the technology to patient studies, said in a statement that they believe “that the method can provide an important diagnostic tool in the treatment of cancer, for example, as CETSA can, in principle, enable us to determine which drug is most effective at targeting the proteins in the tumour. This also makes it possible for clinicians to ascertain at an early stage of treatment whether the tumour has developed a certain kind of resistance and which type of therapy could then be more suitable for the patient.”
From the study abstract in Science:
This cellular thermal shift assay (CETSA) is based on the biophysical principle of ligand-induced thermal stabilization of target proteins. Using this assay, we validated drug binding for a set of important clinical targets and monitored processes of drug transport and activation, off-target effects and drug resistance in cancer cell lines, as well as drug distribution in tissues. CETSA is likely to become a valuable tool for the validation and optimization of drug target engagement.
Article abstract in Science: Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay