Top institutions in the U.S. win Cancer Research UK's Grand Challenge competition

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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