SPECIFICANCER

Challenge

Understand why mistakes in certain genes only cause cancer in specific parts of the body  

Researchers
13
Principal Investigator
Professor Stephen Elledge
Location
The Netherlands, UK and USA
Funded By
Cancer Research UK and the Mark Foundation for Cancer Research - £19m
Specialisms
Genetics, cell biology, bioinformatics, clinical research

Understanding the specifics of cancer  

The past 30 years have identified hundreds of genes that, when mutated, can cause cancer. But the vast majority of these genes only cause cancer in specific parts of the body and not in others – and we don’t know why. By tackling this challenge, SPECIFICANCER could revolutionise our understanding of cancer biology.   

When biology meets cartography

Funded by:

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CRUK Logo
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Mark Foundation

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.   

But 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 only specific places?  

This is where SPECIFICANCER, a diverse, international team of researchers, comes in. By carefully mapping our cells’ cancer drivers – molecules that are known to cause cancer – and their specificity to different tissues, they hope to shed light on which drivers cause cancer in different tissues throughout the body.   

The team’s ambitious plan has the potential to transform our basic understanding of cancer and, ultimately, improve the way we prevent or treat the disease.   

Professor Stephen Elledge, Principal Investigator, SPECIFICANCER

Gregor Mendel Professor of Genetics and of Medicine

We are thrilled to be involved with Cancer Grand Challenges. Understanding the fundamental basis of tissue specificity in cancer is central to generating the most systematic approach to selecting therapies. Cancer Grand Challenges 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.

Going back to basics

Central to SPECIFICANCER’s hypothesis is that cancer develops differently in different organs because of the way they are programmed – for example, a brain cell has a very different function to a skin cell. In both cases, these cells possess the same DNA, but the DNA is organised into a tissue-specific network, dictating a very specific behaviour and function. Understanding how this DNA is programmed is key to understanding the tissue-specifics of cancer.   

The team is driving a range of approaches to understand this – one of which is to home in on basic biology. By scrutinising healthy cells from the 8 tissue types that give rise to the most common cancers – breast, bowel, lung, skin, kidney, liver, brain and pancreas – the team hopes to identify whether certain genes are only active in different parts of the body. They’ll also introduce mutations into hundreds of genes to see which ones drive cancer in the different tissue types.   

Professor Stephen Elledge

The specifics

Eventually, SPECIFICANCER hopes to unite all findings into one comprehensive map of cancer tissue specificity, giving us a complete overview of which genes and molecules play a role in driving cancer in different parts of the body.  

If successful, this map 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.   

A tissue-specific Achilles’ heel  

Through extensive genetic studies to understand how each tissue type is uniquely programmed, SPECIFICANCER’s findings could also reveal why certain treatments are effective in some tumour types, but not in others, and pinpoint tissue-specific targets for drug development.   

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Fran Visco
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Professor Trey Westbrook
Professor Owen Sansom
Professor Peter Park
Professor Richard Marais
Professor Kristian Helin
Dr Kevin Haigis
Dr Teresa Davoli
Professor Hans Clevers
Professor Karen Cichowski
Professor Stephen Elledge, Principal Investigator, SPECIFICANCER