Cancer Dependency Map reveals promising targets for drug development

A comprehensive map of genetic vulnerabilities in cancer has revealed targets for the development of novel anti-cancer drugs.

Scientists from the Wellcome Sanger Institute near Cambridge, and their collaborators, analysed cancer cells in order to develop the second generation of the Cancer Dependency Map. They used the latest in genomics and computational biology and have revealed 370 candidate priority drug targets across 27 cancer types, including for the most prevalent cancers, such as breast, lung, ovarian and colon cancers.

Dr Francesco Iorio, co-lead author of the study, now based at the Computational Biology Research Centre of Human Technopole, Italy, said: 'Analysing the largest-ever cancer dependency dataset, we present the most comprehensive map yet of human cancers' vulnerabilities – their "Achilles heel". We identify a new list of top-priority targets for potential treatments, along with clues about which patients might benefit the most – all made possible through the design and use of innovative computational and machine intelligence methodologies.'

The Cancer Dependency Map was originally developed in 2019 by the Sanger Institute and the Broad Institute, Cambridge, Massachusetts, as an atlas of genetic dependencies and vulnerabilities that increase the risk of an individual developing cancer. This information was aimed to be exploited in the development of new therapies for precision cancer medicine.

Now, by analysing data available from the 930 cancer cell lines within the Cancer Dependency Map and using machine learning methods, the scientists have increased the understanding of what enables cancer cells to grow and survive, and have produced a more comprehensive view of potential new cancer targets in the second generation Cancer Dependency Map.

The researchers first identified the genes, proteins or cellular processes that cancer cells rely on to survive, known as genetic dependencies. They then assessed the occurrence of these targets in cancer patients' tumours and linked them to clinical markers found in the tumours, in order to elucidate which targets might provide the most effective therapies.

Two people might have the same type of cancer, but their diseases can behave differently. That is why we need precision medicine' said Dr Marianne Baker, science engagement manager at Cancer Research UK, who was not involved in the study. 'This ambitious work is a compelling example of research informing drug discovery from the start, paving the way for more effective precision cancer therapies. Giving people treatments for their unique cancer can improve the odds of success and help more people affected by cancer live longer, better lives.'