Drug discovery is such a rapidly changing field that the last decade alone has seen huge leaps in scientific research and technological innovation. Novel drug candidates are consequently improving in quality and safety, enabling more rapid and effective translation to the clinic. Helping to drive these advancements have been opportunities to share the latest innovations and initiate new collaborations, such as at ELRIG’s annual Drug Discovery meeting.
ELRIG Chairman Steve Rees, Vice-President of Discovery Biology at AstraZeneca, describes some of the exciting innovations he has seen in the field over the last decade. He discusses how these are enabling drug discovery research to advance the development of safe and effective therapeutics, and considers what else we can expect over the next 10 years.
How have technologies advanced?
Over the last decade, numerous methodological approaches in drug discovery have progressed to improve the quality and delivery of drug candidates, meaning these candidates are more likely to be translated successfully into new therapies.
A prime example is stem cell technology, which has recently emerged as a new frontier in drug discovery, enabling the creation of microtiter plate-based assays that are predictive of drug toxicity in the clinic. “Perhaps the most impactful examples are assays using stem cell-derived cardiomyocytes, that are used to test compounds for cardiotoxicity,” adds Steve.
Additionally, novel genome editing technologies, such as CRISPR/Cas9, are now enabling the precise alteration of DNA chains and the generation of cell lines to create disease-relevant cellular assays. Steve remarks that using these assays in novel three-dimensional cell-culture systems, along with information-rich detection methods such as confocal imaging, has started to improve the quality of drug candidates.
On top of this, advances in next-generation sequencing (NGS) have enabled genomes to be sequenced for less than $1000, giving even smaller laboratories the chance to understand many diseases at the genetic level.
Steve explains that, “These methods could revolutionise the validation of new drug targets and the identification of safe and efficacious agents that can be delivered into the clinic, which remains one of the major challenges in drug discovery.”
What innovative approaches are enabling crucial breakthroughs?
From a therapeutic perspective, Steve notes that we have made great strides in our understanding of cancer in the last 10 years, which is one of the most dramatic advances he has seen in drug discovery. This progress has been underpinned by several converging innovations.
“The revolution in DNA sequencing methodology has allowed us to understand cancer at the genetic level and is leading to the development of many new medicines,” Steve says.
Alongside this has been the ground-breaking development of novel immunotherapies. These therapies turn patients’ own immune cells into weapons against cancer, and are beginning to help treat individual patient’s diseases more effectively through targeted, personalized therapies.
Steve also recalls the creation of the AstraZeneca Medical Research Council Centre for Lead Discovery in 2014, a unique collaboration in which scientists from AstraZeneca, the Medical Research Council (MRC) and Cancer Research UK (CRUK) work together to discover new medicines.
Marking a recent shift in drug discovery towards synergistic academic-industry collaborations, Steve says, “This partnership has the potential to transform the relationship between AstraZeneca and academia, requiring imagination and vision from leaders at AstraZeneca, the MRC and CRUK to become a reality.”
Staying on top – The role of drug discovery events
It is clear that the world of drug discovery is frequently changing, driving innovation and valuable collaboration to ensure the advancement of effective new therapies. In this rapidly changing field, staying on top of the latest breakthroughs is key to ensuring you can harness all available technologies and approaches to succeed in your research. However, this can sometimes be challenging.
Attending meetings like Drug Discovery 2017 can help. Steve has been a regular delegate at Drug Discovery since it began eleven years ago, serving as program chair for the first six meetings. He explains that, “Scientists engaged in preclinical drug discovery can meet their peers, learn about the latest technology innovations, and hear presentations from world-leading scientists describing the latest advances in drug discovery.”
Steve says that attending Drug Discovery meetings over the last decade has helped to advance his research due to the many unique learning and networking opportunities at the event. In turn, these have enabled him to initiate collaborative drug discovery projects using novel technologies that have revived his research pursuits.
As such, Steve challenges those who attend Drug Discovery 2017 to “see something new in the exhibition hall, hear something new in the presentations, and meet somebody new in the networking events.”
Looking ahead to the next 10 years
We are clearly undergoing a time of dramatic change in the technologies available to drug discovery scientists. Steve looks ahead to the next 5-10 years, predicting that, “Tens of millions of genomes will be sequenced, and precise genome editing technology will develop to become a routine methodology in cellular and animal models. But perhaps the most significant advancement will be in the application of machine learning.”
Machine learning and artificial intelligence technologies are being applied in fields as varied as mapping cellular pathways, automating histology, and lead optimisation chemistry programs. These advances could not only lead to a reduction in cycle time for candidate delivery, but could change how our labs are designed and how our scientists work.
“In the future, I can imagine an environment in which chemists and biologists work in the same laboratory, with an increasing emphasis on applying information technology skills,” Steve says.