The U.S. will lead three new global research projects, tackling some of the biggest challenges in cancer research, it was announced today by Cancer Research UK.
The teams will: investigate how billions of microorganisms living in our bodies, called the microbiome, could be manipulated to treat colorectal cancer; find new ways to tackle cancers caused by chronic inflammation; and develop a deeper understanding of why cancers grow in some tissues but not in others.
These research initiatives will be led by researchers from the Brigham and Women’s Hospital, Harvard Medical School, Boston; Dana-Farber Cancer Institute, Boston; Harvard T.H. Chan School of Public Health, Harvard University, Boston; and the University of California, San Francisco.
Collectively, teams have been awarded around $75 million as part of Cancer Research UK’s Grand Challenge competition – an international funding initiative that aims to answer some of biggest questions facing cancer research*.
Manipulating the microbiome to beat colorectal cancer
Colorectal cancer was estimated to be the third most common cancer diagnosed in both men and women in the U.S. in 2018**, and in recent years there has been a rise in the number of cases seen in younger adults.
There are many lifestyle factors that influence people’s risk of developing the disease. Researchers are discovering that the impact of these factors, such as diet and obesity, on the microbiome may play an important role in colorectal cancer development.
Professor Matthew Meyerson at the Dana-Farber Cancer Institute and Harvard Medical School, and Professor Wendy Garrett at the Harvard T.H. Chan School of Public Health will lead the project, along with researchers in the U.S., Canada, the UK, the Netherlands and Spain, to explore the relationship between the microbiome and colorectal cancer.
The team is aiming to understand the difference between a healthy microbiome and a microbiome associated with cancer and find ways to manipulate this collection of microorganisms to better prevent and treat cancer. They will explore this through clinical trials of new interventions based on the research results.
Professor Wendy Garrett, from the Harvard T.H. Chan School of Public Health, said: “The colon is the most densely populated microbial environment on the planet. We’ve assembled a global team with a lifelong interest in the microbiome and its huge impact on human health. We’ve already seen certain types of bacteria that appear to be associated with a greater risk of colorectal cancer, but that’s just the tip of the iceberg.
“In this project, we hope to answer questions from how the microbiome influences a cancer’s response to treatment, to developing new treatments that alter the microbiome, and understanding how a person’s external environment may affect their microbiome.”
Professor Matthew Meyerson, from the Dana-Farber Cancer Institute and Harvard Medical School, said: “Microbiome research has already thrown up a range of unexpected findings. For example, we’ve found certain bacteria that have spread with cancer cells to other parts of the body. We don’t yet know how this happens, but this is just one of the questions we’ll be trying to answer as part of this project.
“With new genomic technologies, we can map the microbiome in incredible detail, so now is the right time to be investigating this phenomenon of cancer. With this information, we hope to develop new microbiome-targeted therapies for colorectal cancer.”
Finding new ways to tackle cancers linked to chronic inflammation
In another project, Professor Thea Tlsty at the University of California, San Francisco, and collaborators from the U.S., Canada, the UK and Israel will unravel how chronic inflammation is linked to cancer.
Inflammation is part of the body’s immune response. Chemicals released by white blood cells help protect our body from damaged cells, foreign substances or infections. Chronic inflammation can be caused by several factors such as viral and bacterial infections (including colitis), being overweight or lack of exercise, which can lead to more diseases such as cancer. It is suggested that up to 1 in 4 cancers globally are linked to inflammation***.
Recent work shows that the cells surrounding cancers can control whether or not the cancer grows or disappears. The aim is to determine whether it’s possible to treat the inflamed cells and non-cancerous stromal cells (those cells immediately surrounding cancer cells) rather than treating the cancer cells directly.
Professor Thea Tlsty, from the University of California, San Francisco, said: “So far research has mostly focused on cancer cells, but doing this is like tuning into just one side of a conversation. Our project will enable us to hear the other side of that conversation and uncover how the surrounding stromal environment affects cancer development and where inflammation plays a role in this. We can then devise exciting new approaches to treatment from repurposing everyday anti-inflammatory drugs, to designing cells that target cancer-promoting tissues.”
Understanding why cancers grow in some tissues and not in others
Professor Stephen Elledge at Brigham and Women’s Hospital, Harvard Medical School, and collaborators from the U.S., the UK, and the Netherlands are looking to understand why specific genetic defects only affect certain tissues.
Mutations in the BRCA gene are amongst the most well-known inherited genetic defects that can lead to cancer, and increase the risk of breast, ovarian and prostate cancers. There are many other genetic mistakes that increase the likelihood of developing cancer, but why do they only affect certain tissues in the body?
If someone carries a potentially cancer-causing gene mutation, this fault can exist in every cell of the body, but only causes specific cancers, e.g. breast or skin. The team is studying why this is the case, and will use this information to find ways to prevent or treat cancer in these organs.
Professor Stephen Elledge, from Brigham and Women’s Hospital, Harvard Medical School, said: “We think the reason that specific genetic defects cause certain types of cancer comes down to the way different cell types are ‘wired’, and whether the tissue sees it as a ‘GO’ signal or not. We’re going to deconstruct what’s going on by switching cancer genes on and off and tracking the changes in normal, healthy cells from different organs. This will deepen our understanding of the very nature of cancer, and by using cutting-edge technologies like organoids, we hope to find new targets for cancer treatments in future.”
This project is supported in partnership with The Mark Foundation for Cancer Research.
It was estimated that there were around 1,740,000 new cancer cases diagnosed in the United States last year, and around 609,000 deaths from the disease****. Cancer Research UK’s Grand Challenge initiative is harnessing the scientific firepower of world-class researchers and teams to tackle this rising cancer burden, not only in the U.S., but also in the UK and across the world.
Edward Harlow, PhD, member of the Grand Challenge advisory panel and Professor of cancer education and research at Harvard Medical School, said: “I’m not aware of any funding opportunities anywhere in the world that can begin to integrate this many international cancer experts on projects of such clear importance. These teams have been brought together to tackle many of the biggest challenges we currently face in cancer research. We can see from the progress already achieved how powerful it is to support collaborations of this scale.”
Grand Challenge is open to scientists based anywhere in the world and from any discipline to bring innovative, international, and collaborative approaches to research.
The funding for these new projects comes from Cancer Research UK directly and with support from The Mark Foundation for Cancer Research, based in New York, which are providing more than $12.5 million to the project led by Professor Stephen Elledge.
Iain Foulkes, PhD, Cancer Research UK’s executive director of research and innovation, said:
“Individually, these research teams are among the best in the world in their respective fields. By bringing them together across borders, Grand Challenge is enabling these teams to think bigger and establish new and exciting collaborations. The scale of the funding reflects the opportunity we see in harnessing their ability to understand and tackle cancer.”
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For media enquiries contact Carl Alexander in the Cancer Research UK press office on +44 20 3469 8882 or, out of hours, on +44 7050 264 059.
Notes to editor:
* Further information on Cancer Research UK’s Grand Challenge programme can be found at: //cruk.
Funding for teams this round has been possible thanks to a new partnership with The Mark Foundation for Cancer Research, which is half funding the team led by Professor Stephen Elledge.
** Surveillance, Epidemiology, and End Results Program statistics: https:/
*** Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer. 2007 Dec 1;121(11):2373-80.
Okada F. Inflammation-related carcinogenesis: current findings in epidemiological trends, causes and mechanisms. Yonago Acta Med. 2014 Jun;57(2):65-72.
**** Surveillance, Epidemiology, and End Results Program statistics: https:/
More information about the teams:
Manipulating the microbiome to beat colorectal cancer
Lead investigators: Professor Matthew Meyerson, Dana-Farber Cancer Institute and Harvard Medical School and Professor Wendy Garrett, Harvard T.H. Chan School of Public Health
Funding = Up to $25m
Co-investigators:
- Professor Emma Allen-Vercoe, University of Guelph
- Professor Hans Clevers, Hubrecht Institute
- Dr Marios Giannakis, Dana-Farber Cancer Institute, Harvard Medical School
- Professor Robert Holt, BC Cancer Agency
- Dr Curtis Huttenhower, Harvard T.H. Chan School of Public Health
- Professor Kimmie Ng, Dana-Farber Cancer Institute, Harvard Medical School
- Professor Shuji Ogino, Dana-Farber Cancer Institute, Harvard Medical School
- Professor Fiona Powrie, University of Oxford
- Professor Philip Quirke, University of Leeds
- Professor Cynthia Sears, Johns Hopkins University School of Medicine
- Dr Josep Tabernero, Vall d’Hebron Institute of Oncology
- Laura Porter, patient advocate
- David Dubin, patient advocate
The human body is home to trillions of different microorganisms including bacteria, fungi and viruses. Together, they form a community called the microbiota, which differs from organ to organ and person to person. Scientists have shown that these microorganisms have important roles in maintaining human health, but they can also play a role in the development of disease – including cancer.
Professors Matthew Meyerson and Wendy Garrett are leading an international collaboration, spanning five countries, to discover exactly how certain microbes inside the body lead to colorectal cancer and influence a patient’s response to treatment.
By the end of the project, they aim to have revolutionized our understanding of the role the microbiota plays in cancer development, found new ways of preventing colorectal cancer, and defined new treatment strategies through manipulating the gut microbiota.
A new way to tackle cancers caused by chronic inflammation
Lead investigator: Professor Thea Tlsty, University of California, San Francisco
Funding = Up to $25m
Co-investigators:
- Profesor Uri Alon, Weizmann Institute of Science
- Dr Lorenzo Ferri, McGill University
- Professor James Goldenring, Vanderbilt University School of Medicine
- Professor Sui Huang, Institute for Systems Biology, Seattle
- Professor Donald Ingber, Wyss Institute for Biologically Inspired Engineering at Harvard University
- Dr Stuart McDonald, Barts Cancer Institute, Queen Mary University of London
- Professor Garry Nolan, Stanford University
- Professor Morag Park, Goodman Cancer Research Centre and McGill University
- Dr Kole Roybal, University of California, San Francisco
- Dr Doug Winton, Cancer Research UK Cambridge Institute
- Desiree Basila, patient advocate
- David Chuter, patient advocate
- Deborah Collyar, patient advocate
- Ann Russell, patient advocate
Inflammation is the body’s first line of defense – cells of the immune system are recruited to fight dangers, such as infection, and to restore injured tissues back to their original healthy state. This is normally a very tightly controlled process. But sometimes it can spiral out of control and become chronic, aiding the formation of cancer. It is suggested that up to 1 in 4 cancers globally are linked to inflammation.
Professor Thea Tlsty’s team is determined to tackle this problem. Leading a diverse team of experts that spans three continents, she wants to find out whether it’s possible to treat the inflamed cells and tissues surrounding a tumor, rather than directing therapies at the tumor itself.
This Grand Challenge project aims to find novel ways of treating cancer that has been caused by inflammation and develop new options to prevent cancer developing in high-risk patients with chronic inflammatory diseases.
Why cancers grow in some tissues but not others
Lead Investigator: Professor Stephen Elledge, Brigham and Women’s Hospital, Harvard Medical School
Funding = Up to $24m
Co-investigators:
- Professor Karen Cichowski, Brigham and Women’s Hospital, Harvard Medical School
- Professor Hans Clevers, Hubrecht Institute
- Professor Peter Park, Harvard Medical School
- Professor Thomas Westbrook, Baylor College of Medicine
- Dr Kevin Haigis, Beth Israel Deaconess Medical Center
- Professor Kristian Helin, Memorial Sloan Kettering Cancer Center
- Professor Richard Marais, CRUK Manchester Institute
- Professor Owen Sansom, CRUK Beatson Institute, Institute of Cancer Sciences at the University of Glasgow, CRUK Glasgow Centre
- Dr Teresa Davoli, New York University School of Medicine
- Fiona Milligan, patient advocate
- Chris Curtis, patient advocate
- Fran Visco, patient advocate
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. 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.
Professor Stephen Elledge and his international team of researchers 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.
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.
About Cancer Research UK
- Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
- Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
- Cancer Research UK receives no funding from the UK government for its life-saving research. Every step it makes towards beating cancer relies on vital donations from the public.
- Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years.
- Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK’s ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years.
- Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
- Together with its partners and supporters, Cancer Research UK’s vision is to bring forward the day when all cancers are cured.
For further information about Cancer Research UK’s work or to find out how to support the charity, please call 0300 123 1022 or visit //www.
