I recently attended the European Lab Automation conference, put on by Select Biosciences. The event was held June 30th-July 1st in Hamburg, Germany. This was the inaugural conference, combining the traditional topics of high-throughput and high content screening from Screening Europe with other research areas such as biosensors, protein crystallography, agrigenomics, and biobanking. Many podium presentations in the Screening Europe portion of the conference focused on the current state of screening, both high-throughput and high content, in drug discovery and how things would change in the years to come. This was epitomized in a talk entitled “Lead Discovery 2020”, given by Everard Pap, Global Director of Lead Discovery at Sanofi-Aventis. Pap made the point that current screening techniques are many times insufficient, and lead to high failure rates in clinical trials. Lead discovery is “oversimplified, and needs to be translatable”. The current thinking that a disease is controlled by a single target, which can then be modulated by a single selective drug is not working. He also pointed out that there is a need to realize that diseases are an affect of intracellular and intercellular networks. Therefore changes will need to be made in the current model to deal with these insufficiencies. More screening will need to be done in the target identification phase using the most relevant cell models possible, including primary cells. Phenotypic screens, run in a profiling format, will also continue to play a more significant role, to look for epigenetic targets, antibody-based therapeutics (biologics), and biomarkers.
It is interesting to hear more about this change in thinking by major pharmaceutical companies, which will continue to influence global drug discovery trends. Much focus has been placed upon single target screens, examining receptor binding or kinase phosphorylation, in order to find a single selective modulator of the desired event. By emphasizing phenotypic screening in the future, this signals a return to methods used 40 to 50 years ago, when isolated organs were subjected to drugs in order to observe the effect. It will also be curious to see how this shift in thinking will affect reagent vendors, who also have a great deal of time and money invested in assays that look to measure single events. Will this lead to more broad portfolio offerings? Will there come to be a mix of screens run during the target identification phase, or will the single target screens, which have played such a large role in current drug discovery, begin to fade away?
One thing is certain, this change in focus will continue to bring about new opportunities to combine these new screening techniques with appropriate instrumentation to help generate the most in-vivo-like data possible, and eventually help improve the lives of the target patient.
By, BioTek Instruments, Brad Larson, Principal Scientist