Dissecting the tumour specificity of cancer drivers

​ A team of 5 led by Professor Stephen Elledge

The Netherlands and USA 

 Geneticists, bioinformaticians and clinicians

 5 years


Tissue Specificity Grand Challenge

The challenge: Devise approaches to prevent or treat cancer based on mechanisms that determine tissue specificity of some cancer genes.

We are thrilled to be involved in the Cancer Research UK Grand Challenge. Understanding the fundamental basis of tissue specificity in cancer is central to generating the most systematic approach to selecting therapies. The Grand Challenge provides us with the resources to assemble the right team to unravel this riddle and to ensure we are best matching cancer types to the therapies that are most likely to benefit the patient.

Professor Stephen Elledge, Principal Investigator


Cancer is caused by mutations in the DNA of our cells. These mutations can come about by chance, or can be caused by environmental factors, and result in cells multiplying out of control. We know that different DNA mutations can cause different types of cancer. For example, mistakes in the BRCA1 and BRCA2 genes are known to have a role in breast and ovarian cancer development. However, despite decades of research, we don’t yet understand why these errors only cause cancer in specific organs, and not in other parts of the body. The faulty genes can be found in nearly all our cells – so why is the cancer found in specific places?

Professor Stephen Elledge and his international team of researchers are stepping up to the plate, and are looking to answer this question once and for all. By carefully mapping cancer drivers in our cells – molecules that are known to cause cancer – they hope to shed light on which drivers cause cancer in different tissues throughout the body.

In a collaboration that involves researchers from multiple disciplines – including geneticists, cell biologists and bioinformaticians – this Grand Challenge project aims to generate a comprehensive map of cancer drivers and their specificity to different tissues. This has the potential to improve our basic understanding of cancer, and provide information that will impact therapeutic choices for patients.

The Research

The team – made up of researchers in the USA and the Netherlands – are going to look at our cells’ DNA to identify which genes control whether cells divide or not. By looking at the DNA in different locations in the body, this screen will allow the team to look at whether certain genes are only active in specific tissues. This will provide vital information on known cancer drivers, as well as allowing the team to identify new potential drivers of cancer. Alongside this, the researchers will be assessing how well different cancer drugs work in different types of cancer, and if this can be linked to the activity of cancer drivers.


If successful, this map of ‘tissue specificity’ will give us a complete overview of which cancer drivers play a role in the different tissues throughout the body. This understanding could transform the way doctors treat cancer, as they will be able to select which drugs are more likely to work based on exactly how and where the cancer originated.

Headed up by a principal investigator at the cutting edge of his field, this team has set themselves the task to answer a question which has puzzled the cancer community for years. If successful this could revolutionise our basic understanding of what drives cancer and change the way we choose treatment for patients.

Professor René Bernards, Grand Challenge Advisory Panel

The Team


Professor Stephen Elledge

Grand Challenge Shortlisted Team Principal Investigator
Gregor Mendel Professor of Genetics and of Medicine

Country: USA
Organisation: Harvard Medical School
Discipline: Genetics


Professor Karen Cichowski

Professor of Medicine and Genetics

Country: USA
Organisation: Harvard Medical School
Discipline: Medicine


Professor Hans Clevers

Professor of Molecular Genetics

Country: The Netherlands
Organisation: Hubrecht Institute
Discipline: Molecular genetics


Professor Peter Park

Professor of Biomedical Informatics

Country: USA
Organisation: Harvard Medical School
Discipline: Bioinformatics


Professor Trey Westbrook

Professor of Molecular and Human Genetics

Country: USA
Organisation: Baylor College of Medicine
Discipline: Genetics


Dr Kevin Haigis

Director, Cancer Genetics

Country: USA 
Organisation: Beth Israel Deaconess Medical Center
Discipline: Cancer Genetics


Professor Kristian Helin

Director and Professor, Biotech Research and Innovation Centre and Novo Nordisk Foundation for Stem Cell Biology 

Country: Denmark
Organisation: University of Copenhagen
Discipline: Molecular Oncology


Professor Richard Marais 


Country: UK
Organisation: CRUK Manchester Institute
Discipline: Molecular Biology 


Professor Owen Sansom

Director and Senior Group Leader, Deputy Director, Centre Lead

Country: UK
Organisation: CRUK Beatson Institute, Institute of Cancer Sciences at the University of Glasgow, CRUK Glasgow Cancer Centre 
Discipline: Cancer Biology


Dr Teresa Davoli 

Assistant Professor

Country: USA
Organisation: New York University School of Medicine
Discipline: Biochemistry and Molecular Pharmacology

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