How has drug discovery developed in a decade?

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.

With ELRIG’s annual Drug Discovery meeting (3rd-4th October) fast approaching, Steve Rees, Vice-President of Discovery Biology at AstraZeneca and ELRIG Chair, describes some of the exciting innovations he has seen in the field over the last decade and discusses how these are enabling drug discovery research to advance the development of safe and effective therapeutics. Steve also 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 being assays using stem cell-derived cardiomyocytes, that are used to test compounds for cardiotoxicity.

Additionally, novel genome editing technologies, such as CRISPR/Cas9, are now enabling the precise alteration of DNA chains and the generation of gene-edited cell lines to create disease-relevant cellular assays. 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 at a lower cost, giving even smaller laboratories the chance to understand many diseases at the genetic level.

These methods could revolutionise the validation of new drug targets and the identification of well tolerated 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, we have made great strides in our understanding of cancer in the last 10 years, which is one of the most promising advances that we have 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.

Alongside this has been research aiming to turn patients’ own immune cells into weapons against cancer. The goal is to help treat individual patient’s diseases through targeted, personalised therapies.

In addition, the creation of the AstraZeneca Medical Research Council Centre for Lead Discovery in 2014 marks a recent shift in drug discovery towards synergistic academic-industry collaborations. In this unique collaboration, scientists from AstraZeneca, the Medical Research Council (MRC) and Cancer Research UK (CRUK) work together to discover new medicines. This 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.

Looking ahead to the next 10 years

We are clearly undergoing a time of dramatic change in the technologies available to drug discovery scientists. Looking ahead to the next 5-10 years, 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, and will change how our labs are designed and how our scientists work. 

In the future, chemists and biologists may work in the same laboratory, with an increasing emphasis on applying information technology skills.