Cambridge sicentists feature in five of the 10 multidisciplinary teams shortlisted to the final stages of Cancer Research UK's Grand Challenge – an ambitious series of £20m global grants tackling some of the toughest questions in cancer research.
Of the 134 applications sent in, spanning 41 countries, Cancer Research UK has shortlisted 10 multidisciplinary, international teams. The teams will now use £30,000 seed funding to work up their applications for interview later this year.
Dr Meritxell Huch, based at The Wellcome Trust/ Cancer Research UK Gurdon Institute is leading one of the shortlisted projects. She is proposing to investigate how obesity causes cancer and is collaborating with several fellow researchers in Cambridge - Prof Tony Kouzarides, The Gurdon Institute, Prof Ben Simons, Department of Physics, and Mr Kourosh Saeb-Parsy, Department of Surgery.
Research has shown that many types of cancer are more common in people who are overweight or obese, including liver cancer, breast cancer and bowel cancer. But it is not clear exactly how excess fat causes cancer. As obesity is linked to 13 different types of cancer, it’s crucial that we gain knowledge in this area.
Dr Meritxell Huch and her team of world-renowned experts from the UK, The Netherlands, France, Austria and the US will combine their specialist expertise to investigate what’s happening inside our cells when they are exposed to too much fat, and how that can lead to cancer.
On hearing that her project has been shortlisted she said, ‘We are delighted to learn that Cancer Research UK has shortlisted our project. By bringing together a team of clinicians and experts in organoid culture technology, mouse and human genetics and epigenetics, computational biology and genetic engineering, we propose to target the mechanisms by which fat accumulation leads to cancer predisposition, with special attention to liver, colon and breast tumours.’
Using advanced research techniques and technologies, the team will study liver, breast and bowel tissue from cancer patients of a healthy weight, and compare them to samples from patients who are overweight or obese. Delving deep inside the cells of the tissue, the team will analyse and compare the DNA and look for faults in the genes and other cell processes. The complexity of the data and the volume of samples they’ll analyse could give us more information than ever before. With this information, they hope to identify patterns in the genes that could explain how obesity increases the risk of cancer developing and progressing.
The team also plans to investigate how obesity affects fat metabolism – the essential biological process that turns fat into energy. Research has shown that metabolism is faulty in people who are overweight or obese, which could influence their risk of developing cancer.
Another shortlisted project team includes two lworld-leading researchers from Cambridge – Professor Steve Jackson of The Wellcome Trust/ Cancer Research UK Gurdon Institute and Dr John Perry of the MRC Epidemiology Unit. They are looking at finding 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.
The proposed research project seeks to understand how chronic inflammation contributes to the development of cancers, focusing initially on chronic inflammation and colitis in inflammatory bowel disease, which are known risk factors for bowel cancer.
Inflammation is an important process in the immune system’s fight against infection and injury – molecules and cells of the immune system help to protect the body and restore damaged tissues. But excess inflammation can cause serious harm, ultimately damaging and destabilising chromosomes – the structures that assemble around a cell’s DNA. This can alter the way the cell behaves, increasing the risk of it growing out of control and becoming cancerous. Different chronic inflammatory diseases can put a person at higher risk of developing a range of cancers, such as pancreatic, liver, gastric and bowel cancer.
The team hypothesise that stress and damage to cells of the intestinal mucosa due to inflammation elevates chromosomal instability. Chromosomal instability, where either whole chromosomes or parts of chromosomes are duplicated or deleted, is found in over 80% of cases of both inflammatory bowel disease and bowel cancer. By unravelling the molecular mechanisms involved in these processes using innovative genomic analysis and cell-based studies, mouse models of disease and human clinical samples, they hope to speed up the identification of new ways to diagnose and prevent these diseases, and to develop new therapies.
Dr John Perry of the MRC Epidemiology Unit at the University of Cambridge, who will be undertaking an analysis of alterations in gene and chromosome structure in over 1 million individuals as part of this project, said:
“I’m excited to be part of a multi-disciplinary team using state-of-the-art experimental approaches to answer basic questions in cancer biology. Understanding how inflammation leads to errors in cell division has the potential to identify new pathways to target for future therapies.”
Professor Steve Jackson, who will explore, in mouse models of inflammatory bowel disease, how their discoveries about chromosomal instability can be used to treat cancer, said: "I am delighted that our application has made the shortlist and hope that we are successful at the next stage!".
A third shortlisted team, also looking at inflammation and cancer, includes Dr Doug Winton based at the Cancer Research UK Cambridge Institute. This project is hoping 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.
Led by Professor Thea Tlsy at the University of California, the team plans to utilise the type of cells that naturally thrive in and around a tumour, and engineer these cells to release therapeutic agents. But rather than targeting the tumour itself, these therapies will be directed at the tumour’s neighbouring cells and tissues – restoring chronically inflamed tissues to a healthy state. The team wants to find out whether this approach will gradually guide tumour cells back to a non-cancerous, benign state, or help prevent the tumour from growing further. If so, the tumour cells will be less likely to initiate survival mechanisms that can hinder therapy – and therefore respond well to treatment aiming to shrink the tumour in the future.
A fourth shortlisted team includes Dr Raj Jena from Cambridge University Hosptitals. Led by Trevor Esward, Sara Faithfull and their team from the UK and the Netherlands they have proposed a new way to identify the early signs of cancer – by analysing people’s consumer and behavioural habits.
This Grand Challenge project aims to bring together consumers, patients, and their social groups with a multi-disciplinary research team. They plan to use machine-learning technology to identify changes in behaviour that might indicate if a person has cancer and to address the ethical and privacy issues of accessing personal data. This will enable those with early signs of cancer to get support from healthcare practitioners.
Professor Wolf Reik from the Babraham Institute, is part of a fifth shortlisted team. Their project aims to eliminate sleeping cancer cells. Cancer cells that were not killed by initial, seemingly effective treatment, can go to sleep and hide in a dormant state in distant organs or bones, escaping detection. Often without warning, these dormant cells can wake up many months or years later and start to form a new cancer. It is not known why or how this happens, making these returning cancers hard to predict, detect and treat.
Led by Professor Peter Croucher, from the Garvan Institute of Medical Research in Australia, this international team of cancer biologists, immunologists, geneticists, haematologists and oncologists aims to create a map of the biological environment around dormant cancer cells and the processes that control them, so that treatments can be developed to stop cancer returning.