Scientists use DNA-editing tool CRISPR to catalogue cancer’s weaknesses

In collaboration with the Press Association

UK scientists are putting together a list of the most promising potential cancer drug targets in one of the largest lab studies of its kind.

Scientists at the Wellcome Sanger Institute are no strangers to big datasets, having played a vital role in reading the code of the first human genome.

They’re now using these skills to identify key areas of cancer cells’ DNA code (genes) that are essential for their survival.

Publishing their latest work in the journal Nature, the team used DNA-editing technology called CRISPR to find and rank genes that could be promising drug targets, which could help to focus future drug development.

The vast amounts of data are being combined with other research to build a complete map of all the genes cancers depend on to grow.

Professor Karen Vousden, Cancer Research UK’s chief scientist, said: “What makes this research so powerful is the scale. CRISPR provides a unique tool to accelerate discovery of oncology drug targets, and this study is a salient leap in a positive direction.”

Big science

Scientists used CRISPR technology, which can precisely seek out and alter specific regions of a cell’s DNA, to switch off every gene, one-by-one, in over 300 different types of lab-grown cancer cells.

The lab-grown cells spanned 30 different types of cancer, including common cancers, like bowel and breast, and those that are hard to treat and have poorer survival, such as lung and pancreatic cancer. 

From these results the team were able to rank and prioritise 600 promising drug targets.

Although the study represents the very early stages of this research, the aim is to use this data to prioritise and help speed up the development of more effective treatments.

Dr Francesco Iorio, one of the study’s lead researchers from the Wellcome Sanger Institute and Open Targets, said that to give a new drug the best chance of succeeding, it’s crucial to select the best and most promising drug target at the beginning of the drug development process.

“For the first time, in a data-driven way, we provide guidance at a genome-scale on which new therapeutic targets should be put forward for the development of new anti-cancer drugs,” he said.

Just the beginning

Despite huge progress, surgery, chemotherapy and radiotherapy remain as cornerstone treatments for many cancers.

But cancers can be different from patient to patient and not everyone will respond to these treatments. Healthy cells can also be killed during treatment, leading to side effects.

It’s hoped that a more targeted approach might enable researchers to develop effective new treatments that selectively kill cancer cells and leave healthy cells unharmed. 

The researchers will make the data publicly available for other scientists to access and learn from.

Dr Mathew Garnett, who leads the project at the Wellcome Sanger Institute, said: “This tool will be freely available for scientists across the world to understand what makes a cancer a cancer, and how we might target different types of cancers much more effectively than we do today."

But while the results are promising, Vousden said it was important to remember that studying cells in the lab doesn’t always reflect the complexities of cancer in the human body.

“This work provides some excellent starting points and the next steps will be a thorough analysis of the genes that have been identified as weaknesses in this study, to determine if they will one day lead to the development of new treatments for patients," she added.

References

Behan F, et al. (2019) Prioritisation of cancer therapeutic targets using CRISPR-Cas9 screens. Nature. DOI: 10.1038/s41586-019-1103-9