Dissecting the tumour specificity of cancer drivers
A team of 5 led by Professor Stephen Elledge
The Netherlands and USA
Geneticists, bioinformaticians and clinicians
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 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
Professor Stephen Elledge
Grand Challenge Shortlisted Team Principal Investigator
Gregor Mendel Professor of Genetics and of Medicine
Organisation: Harvard Medical School
Professor Karen Cichowski
Professor of Medicine and Genetics
Organisation: Harvard Medical School
Professor Hans Clevers
Professor of Molecular Genetics
Country: The Netherlands
Organisation: Hubrecht Institute
Discipline: Molecular genetics
Professor Peter Park
Professor of Biomedical Informatics
Country: Harvard Medical School
Professor Trey Westbrook
Professor of Molecular and Human Genetics
Country: Baylor College of Medicine