Cancer Research UK shortlists teams for £20m Grand Challenge to tackle cancer’s toughest problems

ENDS

Contacts for shortlisted teams’ institute press offices:

• For Professor Roy Bicknell please contact – [email protected] / 0044 121 414 5134
• For Professor Alan Rickinson please contact – [email protected] / 0044 121 414 5134
• For Dr Jelle Wesseling please contact – [email protected]
• For Professor Mike Stratton please contact – [email protected] / 0044 1223 492 368
• For Professor Freddie Hamdy please contact – [email protected] / 0044 1865 270 046
• For Dr Josephine Bunch please contact – [email protected] / 0044 20 8943 8669
• For Dr Surinder Sahota please contact – [email protected] / 0044 2380 593 212
• For Professor Gregory Hannon please contact – [email protected] / 0044 1223 769 702
• For Professor Ehud Shapiro please contact – [email protected] / 00972 8934 3856

Notes to editor:

* See website for more information: http://www.cancerresearchuk.org/funding-for-researchers/how-we-deliver-research/grand-challenge-award

** Lay summaries of shortlisted teams’ projects:

Eradicating cancer by vaccination against the tumour blood supply (Grand Challenge 1: Develop vaccines to prevent non-viral cancers)

Lead investigator: Professor Roy Bicknell, University of Birmingham, UK

Co-investigators:

Dr George Coukos, Ludwig Institute for Cancer Research, USA  

Professor Michele De Palma, Swiss Institute for Experimental Cancer Research, Switzerland

Professor Arjan Griffioen, VU University Medical Centre, The Netherlands         

Professor Douglas Hanahan, Swiss Institute for Experimental Cancer Research, Switzerland

Dr Stephen Hodi, Dana-Farber Cancer Center/Broad Institute, USA

Professor Gary W. Middleton, University of Birmingham, UK      

Dr Anna-Karin Olsson, Uppsala University, Sweden         

The process of blood vessel formation in tumours has long been of interest to cancer researchers because it’s regarded as an Achilles heel for the disease: a tumour can’t grow to a size that’s potentially harmful unless it establishes its own blood supply. 

Professor Roy Bicknell and an international team of researchers want to exploit this characteristic by using it as a target for a vaccine that can prevent non-viral cancers. It’s a tough challenge and one that requires a wide-range of expertise. So the team is bringing together scientists with a long track record in studying blood vessel formation alongside global experts in vaccine development and clinical trials.

Members of the team have already identified target molecules specific to this process in cancer – a Grand Challenge award would be used to establish which of these molecules make the best vaccine target before building a vaccine and testing it for the first time in people at an increased risk of cancer. The hope is that the vaccine will instruct the immune system to destroy these cancer-specific molecules whenever they arise, stopping tumours in their tracks before they start to grow.

Ending EBV cancers (Grand Challenge 2: Eradicate EBV-induced cancers from the world)

Lead investigator: Professor Alan Rickinson, University of Birmingham, UK

Co-investigators:

Professor Anthony Chan, Chinese University of Hong Kong, China

Professor Hans Clevers, Hubrecht Institute, The Netherlands

Dr Jeff Cohen, National Institutes of Health, USA

Professor Masashi Fukayama, University of Tokyo, Japan

Dr Steve Gottschalk, Baylor College of Medicine, USA

Professor Paul Lehner, University of Cambridge, UK

Dr Paul Lieberman, Wistar Institute, USA

Dr Christian Munz, University of Zurich, Switzerland

Dr Cliona Rooney, Baylor College of Medicine, USA

Professor Ugur Sahin, TRON Translational Cancer Center, Germany

Professor Andreas Strasser, Walter and Eliza Hall Institute, Australia

Grand Challenge 2 is to eradicate the 200,000 cases of cancer that occur every year worldwide because of infection with the Epstein Barr virus (EBV). Professor Alan Rickinson and his team are proposing to attack EBV cancers on two fronts: transforming treatment for patients with existing cancers and, in future, protecting people from ever catching the virus. 

Rickinson’s own group have been at the forefront of EBV research for several decades and recently received Cancer Research UK’s Translational Cancer Research Prize for their efforts that culminated in the first therapeutic vaccine for EBV-related cancers to reach the clinic.

A Grand Challenge award would build on this, bringing together for the first time a stellar team of cell biologists, virologists, immunologists and clinical investigators to further develop emerging treatments, to devise entirely new therapeutic approaches, and to work towards a vaccine that will rid the world of EBV cancers by preventing infection with the virus.

An early warning system for cancer: linking mutational signatures back to the events that caused them (Grand Challenge 3: Discover how unusual patterns of mutation are induced by different cancer-causing events)

Lead investigator: Professor Mike Stratton, Wellcome Trust Sanger Institute, UK

Co-investigators:

Dr Ludmil Alexandrov, Los Alamos State Laboratory, USA

Dr Allan Balmain, UCSF, USA

Dr Paul Brennan, IARC, France

Dr Peter Campbell, Wellcome Trust Sanger Institute, UK

Professor Stephen Jackson, Wellcome Trust Sanger Institute, UK

Professor David Phillips, King’s College London, UK

For complicated cancer risks like obesity, pinning down the exact mechanism by which they cause cancer at a molecular level is a challenge. Professor Sir Mike Stratton’s team intend to address this on a grand and global scale.

First, to understand the geographical differences in cancer incidence they’ll work backwards to study the DNA signatures from thousands of cancers where lifestyle factors, such as obesity and alcohol consumption, are known to increase risk. Then they’ll combine this with lab-based research to build the most comprehensive picture we’ve ever had of signatures linked to different cancers and carcinogens.

Their ultimate goal is to be able to monitor an individual’s DNA signature and provide an early warning system that a cancer-causing event may have occurred, so that it might be possible to prevent, reverse or control the cancer risk before it has a chance to accumulate.

When is cancer not really cancer? (Grand Challenge 4: Distinguish between lethal need treating and non-lethal cancers that don’t)

Lead investigator: Dr Jelle Wesseling, Netherlands Cancer Institute, The Netherlands

Co-investigators:

Dr Adele Francis, University Hospitals Birmingham NHS Trust, UK

Dr Phillip Andrew Futreal, MD Anderson Cancer Center, USA

Dr Shelley Hwang, Duke University School of Medicine, USA

Dr Jos Jonkers, Netherlands Cancer Institute, The Netherlands

Dr Serena Nik-Zainal, Wellcome Trust Sanger Institute, UK

Professor Alastair Mark Thompson, MD Anderson Cancer Center, USA

Ductal carcinoma in situ (DCIS) is regarded as a ‘pre-cancerous’ state in breast cancer, and accounts for a quarter of what is diagnosed through screening as ‘breast cancer’. With existing detection methods it is impossible to accurately distinguish between DCIS that will do no harm and doesn’t require treatment and DCIS that will progress to invasive breast cancer. Consequently, many women with harmless DCIS are overtreated.

Dr Jelle Wesseling, breast pathologist at the world-renowned Netherlands Cancer Institute, has brought together an international team, collectively having access to a unique collection of breast samples and data helping to address this challenge.

Their goal is to identify the key features that predict how DCIS will evolve. The results could be twofold: confidence that a DCIS ‘cancer’ can be left alone, and molecules that could be targeted along the timeline of progression from DCIS to halt the development of breast cancer.

Can multiple myeloma help us determine what makes a cancer lethal? (Grand Challenge 4: Distinguish between lethal need treating and non-lethal cancers that don’t)

Lead investigator: Dr Surinder Sahota, University of Southampton, UK

Co-investigators:

Dr Madhav Dhodapkar, Yale Cancer Center, USA

Professor Claire Edwards, University of Oxford, UK

Dr Dirk Hose, Heidelberg University, Germany

Dr Jose Ignacio Martín-Subero, Consorci Institut D’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain

Dr Oscar Yanes, Universitat Rovira i Virgili, Spain

Transformation of a benign blood cancer described as asymptomatic gammopathy (ASG) to fatal multiple myeloma (MM) provides a unique paradigm to understand onset of malignant disease. The challenge is knowing if and when this switch will occur, and how to test for it in asymptomatic patients.

Bringing together world-leading experts in immunogenetics, genetics, blood and bone cancer, and biochemists, UK-based researcher Dr Surinder Sahota proposes using the transition from ASG to MM as a unique model in which to interrogate the evolution of fatal disease. His team will look at a wide-ranging spectrum of tumour and microenvironment characteristics, at the molecular and cellular global levels, to establish what exactly tips the balance towards malignant disease.

Identifying this trigger would be enormously beneficial for the 80,000 people worldwide who die from myeloma each year, but may also identify transition traits that other cancers may go through to become lethal.

Lethal vs non-lethal prostate cancer: distinguishing the tigers from the pussycats (Grand Challenge 4: Distinguish between lethal need treating and non-lethal cancers that don’t)

Lead investigator: Professor Freddie Hamdy, University of Oxford, UK

Co-investigators:

Professor George Bova, Tampere University, Finland

Professor Colin Cooper, University of East Anglia, UK

Professor Johann de Bono, The Institute of Cancer Research, UK

Professor Ros Eeles, The Institute of Cancer Research, UK

Professor Charlie Swanton, Francis Crick Institute/University College London, UK

Dr Andrew Vickers, Memorial Sloan-Kettering Cancer Center, USA

Professor Tapio Visakorpi, BioMediTech, Finland

Dr David Wedge, Oxford Big Data Institute, UK 

Since 2001, Professor Freddie Hamdy has been leading one of the largest prostate cancer treatment trials in the world.  Now, he’s poised to lead a team to address one of the biggest challenges in the world: how to distinguish between a lethal prostate cancer and one that doesn’t need treatment.

The team brings unparalleled access to patient samples and data from several of the world’s largest and longest-running prostate cancer trials. The answer to what is distinct about a lethal prostate cancer is almost certain to be found within.

The team will combine detailed molecular analysis of existing samples with novel lines of investigation in new patient groups – aiming to understand what biological features are present at the earliest point when cancer spreads or becomes resistant to treatment.

The overall goal is to reduce unnecessary treatment of ‘safe’ cancers, and ensure rapid and thorough treatment of those likely to be lethal. The team hope to develop and test a ‘molecular checklist’ of features that will make this a reality.

Charting unknown territory: mapping what we don’t know about a tumour (Grand Challenge 5: Find a way of mapping tumour at the molecular and cellular level)

Lead investigator: Dr Josephine Bunch, National Physical Laboratory, UK

Co-investigators:

Dr Richard Goodwin, AstraZeneca, UK

Dr Ian Gilmore, National Physical Laboratory, UK

Dr Heidi Goenaga Infante, LGC Ltd, UK

Dr George Poulogiannis, The Institute of Cancer Research, UK

Professor Owen J Sansom, Cancer Research UK Glasgow Institute, UK

Professor Zoltan Takats, Imperial College London, UK

Dr Mariia Yuneva, Francis Crick Institute, UK

Analytical Chemist Dr Josephine Bunch and her team would argue that if you want to map the true picture of a tumour, you need to start with the parts you don’t know – rather than looking for what you do.

Bunch and colleagues at the National Physical Laboratory have pioneered techniques that can image thousands of molecules in cells and tissues simultaneously. The technology is so powerful that it can zoom in to show the location of single molecules within individual cells.

Their Grand Challenge proposal sees them teaming up with world leaders in tumour metabolism, imaging and modelling to apply this technology to the cancer field.

They hope to develop the technology to a stage where it can visualise the rewiring of cellular and metabolic networks that occurs at different stages of tumour progression: an invaluable tool that could identify new treatment targets and more accurately characterise and monitor patients’ disease.

Building a virtual reality interactive map of breast cancer (Grand Challenge 5: Find a way of mapping tumour at the molecular and cellular level)

Lead investigator: Professor Greg Hannon, University of Cambridge, UK

Co-investigators:

Dr Johanna Joyce, Ludwig Institute for Cancer Research, Switzerland

Dr Samuel Aparicio, British Columbia Cancer Agency, Canada

Professor Shankar Balasubramanian, University of Cambridge, UK

Professor Edward S. Boyden, Massachusetts Institute of Technology, USA

Professor Carlos Caldas, University of Cambridge, UK

Owen Harris, DEEP VR, Ireland

Professor Simon Tavaré, University of Cambridge, UK

Dr Nicholas Walton, University of Cambridge, UK

Imagine if you could literally step inside a tumour and have a good look around, appreciating everything that is going on around you – this is the vision for Professor Greg Hannon’s experiential approach to Challenge Five.

The goal is to develop and combine precise, 3D maps of tumours and their environment in a virtual reality experience, allowing researchers to ‘walk around’ inside a tumour, visualising how individual cells adapt to their environment.

The initial focus is on breast cancer – a complex disease that has at least 10 distinct subtypes. Maps will be generated using a combination of approaches, from imaging to cell-tracking, and will be matched with information on how the tumours respond to treatment.

This approach will provide an entirely new way for scientists and doctors to understand how each cancer develops and predict how it’s affected by treatment, and could change the way patients are diagnosed and treated.

Creating a 4D cancer atlas to track cancer’s journey (Grand Challenge 5: Find a way of mapping tumour at the molecular and cellular level)

Lead investigator: Professor Ehud Shapiro, Weizmann Institute of Science, Israel

Co-investigators:

Dr Ido Amit, Weizmann Institute of Science, Israel           

Professor Caroline Dive, the Cancer Research UK Manchester Institute, UK

Dr Levi Garraway, Dana-Farber Institute, USA

Dr John Marioni, Cancer Research UK Cambridge Institute, UK  

Professor Chris Ponting, University of Edinburgh, UK     

Dr Aviv Regev, Broad Institute, USA       

Professor Charles Swanton, UCL Cancer Institute/Crick Institute, UK

Professor Amos Tanay, Weizmann Institute of Science, Israel      

Nearly all cancer deaths are caused by the disease spreading metastases beyond the original tumour. Professor Ehud Shapiro from the Weizmann Institute of Science and his team propose to develop a method for generating personalised 4D atlases of cancers. Each atlas will reveal the 3D structure of the tumour and its metastases in exquisite detail. It will also depict the 4th dimension – time – showing the tumour’s origins and how its cells evolved, spread metastases and developed resistance.

By transforming each atlas resulting from their in-depth cellular analysis into a 4D virtual reality scenario, a vivid portrayal of each cancer’s growth over time and space will be created, with the patient’s body as the theatre and the cancer cells as ‘actors’ within.

This approach will provide unprecedented knowledge of the origin and spread of cancer, forming the basis for more effective diagnostic tools and treatments.