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Cancer's genetic vulnerabilities revealed

Thursday April 11th, 2019

British scientists have found thousands of genes linked to the survival of cancer in the largest research project of its kind, it was announced last night.

The researchers said they had picked out 600 genetic variants that showed the most promise as targets for new drugs.

The Wellcome Sanger Institute, Cambridge, UK, and another research organisation, Open Targets, published their findings in Nature last night.

The scientists say the used CRISPR technology to "disrupt" every gene in more than 300 models of cancer from 30 types of cancer. This involved nearly 20,000 genes.

They have called their findings the Cancer Dependency Map, as it outlines the cancer's vulnerabilities.

The cancers in the study included the most common – lung, colon and breast – together with those that are currently the hardest to treat, such as those of the ovaries, lung and pancreas.

The "top scoring" target found in several different cancers was the Werner syndrome RecQ helicase - WRN, they report. Cancers that are microsatellite unstable – because of faulty DNA repair pathways – need WRN for survival, they report.

Researcher Dr Mathew Garnett, from the Wellcome Sanger Institute and Open Targets, said: “The Cancer Dependency Map is a huge effort to identify all the weaknesses that exist in different cancers so we can use this information to empower the next generation of precision cancer treatments.

"Ultimately we hope this impacts on the way we treat patients, so many more patients get effective therapies. In the meantime, 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.”

Fellow researcher Dr Fiona Behan said: “With the Cancer Dependency Map, I really hope to revolutionise treatment for patients. I didn’t get in this game to generate long lists of priority targets, I want to make a difference in a patient’s life.

"Even a handful of new, more effective anti-cancer drugs in the clinic or an improvement in the drug development process as a result of this research would benefit an enormous number of patients.”

The Charity Cancer Research UK said the work was a "salient leap."

Chief scientist Professor Karen Vousden added: "We should remember that studying cells in the lab doesn’t always reflect the complexities of cancer in the human body and so will not necessarily reflect how someone will respond to a drug.

"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.”

Fiona Behan et al. Prioritisation of cancer therapeutic targets using CRISPR-Cas9 screens. Nature 10 April 2019; doi: 10.1038/s41586-019-1103-9

https://www.nature.com/articles/s41586-019-1103-9

Tags: Cancer | Genetics | UK News | Women's Health & Gynaecology

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