Understand why mistakes in certain genes only cause cancer in specific parts of the body
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
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.
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.
Helen has been involved in patient advocacy since her breast cancer diagnosis and treatment in 2017. She is research and science advisor for the breast cancer patient advocacy group, Met-UP UK. A scientist herself, Helen is passionate about improving communication between patients and scientists, particularly in basic research.
Fran Visco is a more than 30-year survivor of Breast Cancer. She brings over 25 years of advocacy experience to the team as President of the National Breast Cancer Coalition (NBCC), an advocacy coalition of hundreds of organizations and tens of thousands of individual members. Ms. Visco previously served three terms on the President’s Cancer Panel Special Commission on Breast Cancer and was the first consumer to chair the Integration Panel of the Department of Defense Peer-Reviewed Breast Cancer Research Program. She co-chaired the National Action Plan on Breast Cancer and served on the National Cancer Policy Board. She lectures nationally and internationally on the politics of breast cancer and women’s health advocacy issues. She also offers scientific and governmental policy presentations to research, governmental and scientific entities.
President, National Breast Cancer Coalition
Baylor College of Medicine
Professor Owen Sansom is interim director of the Cancer Research UK Beatson Institute. He has published over 200 papers in a research career spanning 16 years. Owen gained his PhD in 2001 working on in vivo models of apoptosis in cancer. Since then, Owen has been instrumental in determining the molecular hallmarks and cell of origin of epithelial cancers (colorectal and pancreatic).
Using this experience, the Sansom laboratory will provide the Grand Challenge team with the in vivo models that will be mapped in 3D.
Cancer Research UK Beatson Institute
Harvard Medical School
CRUK Manchester Institute
Memorial Sloan Kettering Cancer Centre, Sloan Kettering Institute
Dana–Farber Cancer Institute
Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology
Hans obtained his MD and PhD from Utrecht University, Holland. He has been a Professor in Molecular Genetics at Utrecht University since 1991. He runs his lab in the Hubrecht Institute. Throughout his career, he has worked on the role of Wnt signalling in stem cells and cancer.
His discoveries include TCF as Wnt effector, the role of Wnt in adult stem cell biology and of Wnt pathway mutations in colon cancer, Lgr5 as a marker of adult stem cells, and –finally- a method to grow ever-expanding mini-organs (‘organoids’) from Lgr5 stem cells derived from a range of healthy or diseased human tissues. This has led to over 700 publications and >120,000 citations. He is member of the Royal Netherlands Academy of Arts and Sciences, National Academy of Sciences of the USA, Academie des Sciences (Paris) and Royal Society London. Recipient of multiple awards, including the Swiss Louis Jeantet Prize, the Heineken Prize, and the Breakthrough Prize in Life Sciences.
Brigham and Women’s Hospital, Harvard Medical School
Brigham and Women’s Hospital, Harvard Medical School