Cancer gene targets found and ranked using CRISPR

UK scientists have used genome-editing  to identify hundreds of potential drug targets for new cancer treatments.

In one of the largest studies of its kind, the team at the Wellcome Sanger Institute, Cambridge, pinpointed key areas of cancer cell DNA necessary for cell survival. They then developed a new computational system to select the most promising targets for drug treatment. The results could help accelerate the development of more effective, targeted cancer therapies.

'To give a new drug the best chance of succeeding in the very final phases of clinical trials, it is crucial to select the best and most promising drug target at the beginning of the drug development process,' said study co-author Dr Francesco Iorio, from the Wellcome Sanger Institute and Open Targets, Cambridge.

'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.'

In the new study, published in the journal Nature, the researchers used CRISPR to switch off almost 20,000 genes, one at a time, in more than 300 different types of lab-grown human cancer cells. The cells lines were grown from 30 different cancer types, from 19 different tissues. The results revealed 6000 genes that were crucial to the survival of at least one type of cancer.

The team produced a shortlist of 600 potentially suitable drug targets by disregarding genes that are also needed for the survival of healthy cells and those already being targeted by precision drugs. Developing new precision cancer therapies that kill cancer cells while leaving healthy cells undamaged will help avoid unwanted side effects that typically occur with common cancer treatments, such as chemotherapy and radiotherapy, which affect cells throughout the body.

It is hoped the findings of the study will help speed up the development of new and more effective treatments for cancer patients, as well as reduce the costs involved in the early stages of drug development.

Professor Karen Vousden, chief scientist at Cancer Research UK, commented that it was important to remember that studying cells in the lab didn't always reflect the complexities of cancer in the human body. But the study provided some excellent starting points, she 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,' Professor Vousden concluded.