Shortlisted teams 2016

Grand Challenge phase 2

Challenge 1
Develop vaccines to prevent non-viral cancers
Return
1
Prof. Alan Rickinson
Challenge 2
Challenge 2
Eradicate EBV-induced cancers from the world
Return
Challenge 3
Discover how unusual patterns of mutation are induced by different cancer-causing events
Return
Challenge 4
Distinguish between lethal cancers that need treating, and non-lethal cancers that don’t
Return
Challenge 4
Distinguish between lethal cancers that need treating, and non-lethal cancers that don’t
Return
5
Dr Jelle Wesseling
Challenge 4
Challenge 4
Distinguish between lethal cancers that need treating, and non-lethal cancers that don’t
Return
Challenge 5
Find a way of mapping tumours at the molecular and cellular level
Return
Challenge 5
Find a way of mapping tumours at the molecular and cellular level
Return
Challenge 5
Find a way of mapping tumours at the molecular and cellular level
Return

Eradicating cancer by vaccination against the tumour blood supply

Prof. Roy Bicknell (University of Birmingham)
Dr George Coukos (Ludwig Institute for Cancer Research)
Prof. Arjan Griffioen (VU University Medical Centre)
Dr Anna-Karin Olsson (Uppsala University)
Dr Stephen Hodi (Dana-Farber Cancer Center/Broad Institute)
Prof. Michele De Palma (Swiss Institute for Experimental Cancer Research)
Prof. Gary W. Middleton (University of Birmingham)
Prof. Douglas Hanahan (Swiss Institute for Experimental Cancer Research)
Jacqui Gath

Summary:

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.

Grand Challenge allows us, for the first time, to tackle the development of a universal cancer vaccine, something that would never be funded by other schemes as it would be deemed too difficult or high risk. It is this balance of accepting high risk elements to achieve great progress that makes Grand Challenge so exciting Prof. Roy Bicknell, University of Birmingham
I am excited about the approach of creating a vaccine that targets the tumour micro-environment as it could have huge clinical impact for many cancers. Novel strategies like this, turning traditional tactics on their heads, can make good science great Prof. Adrian Bird, University of Edinburgh
Jim Elliot
What is exciting about this proposal is that it is looking to combine both treatment and prevention as well as using the body's own defence mechanism, the immune system, to do this and so would potentially lead to a treatment that is both safe with little, if any, wider side effects and would be long lasting Jim Elliott, Grand Challenge Patient Advisory Panel

Ending EBV cancers

Prof. Alan Rickinson (University of Birmingham)
Dr Cliona Rooney (Baylor College of Medicine)
Dr Steve Gottschalk (Baylor College of Medicine)
Prof. Hans Clevers (Hubrecht Institute)
Prof. Andreas Strasser (Walter and Eliza Hall Institute)
Dr Paul Lieberman (Wistar Institute)
Prof. Dr Ugur Sahin (TRON Translational Cancer Center)
Dr Christian Munz (University of Zurich)
Prof. Masashi Fukayama (University of Tokyo)
Prof. Anthony Clan (Chinese University of Hong Kong)
Dr Jeff Cohen (National Institutes of Health)
Prof. Paul Lehner (University of Cambridge)
To be confirmed

Summary:

Grand Challenge Two 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.

Alan Rickinson
The Grand Challenge is a huge opportunity for our newly-assembled global team. Such support would take research on EBV to a new level and make possible the goal of eliminating the many cancers linked to this virus Professor Alan Rickinson, Birmingham University
Chris Wild
This team is ambitious and bold. Their integrated approach brings together a wide range of expertise and technology to take on the tough challenge of eradicating EBV induced cancer Dr Chris Wild, Director of IARC
Terry Kavanagh
I particularly welcome Professor Rickinson’s Challenge to develop a vaccine that can be used both as a treatment and a preventive measure for EBV. This research could also have a knock on effect giving support to the development of vaccines for other types of cancer Terry Kavanagh, Grand Challenge Patient Advisory Panel

An early warning system for cancer: linking mutational signatures back to the events that caused them

Prof. Sir Mike Stratton (Wellcome Trust Sanger Institute)
Dr Paul Brennan ( IARC)
Dr Ludmil Alexandrov (Los Alamos State Laboratory)
Dr Allan Balmain (UCSF)
Prof. Stephen Jackson (Wellcome Trust Sanger Institute)
Prof. David Phillips (King's College London)
Dr Peter Campbell (Wellcome Trust Sanger Institute)
Mimi McCord (Heartburn Cancer UK) and Maggie Blanks (Pancreatic Cancer Research Fund)

Summary:

There are big differences in cancer incidence between different parts of the world and the reasons for many of these remain unknown. Even where previous research suggests that complicated risk factors like obesity contribute, pinning down the mechanisms by which they cause cancer at a molecular level is challenging. Professor Mike Stratton’s team intend to address this on a grand and global scale.

To understand the geographical differences in cancer incidence they will study the DNA of thousands of cancers from carefully chosen locations around the world to uncover the “mutational signatures” left decades before by the environmental exposures and lifestyle practices responsible for the differences. They will combine this with lab-based research, building a comprehensive picture of the mutational signatures due to the hundreds of known and suspected human carcinogens, which they will then compare with those found in the cancers.

Their ultimate goal is to monitor these DNA signatures in healthy individuals to provide an early warning system that unsuspected exposures to cancer-causing agents have occurred, so that it might be possible to control the cancer risk before it has a chance to accumulate further.

Prof. Sir Mike Stratton
We’re thrilled to be shortlisted for Cancer Research UK’s Grand Challenge and to have been given the opportunity to bring together expertise in epidemiology and carcinogenesis complemented by Sanger’s large-scale genomics platforms. Cancer is a global problem and needs these large funding initiatives to deliver a step change in our understanding - an understanding which will allow us and others to develop new and better treatments and innovative, evidence-based prevention strategies. Prof. Sir Mike Stratton, Wellcome Trust Sanger Institute
Prof. Tyler Jacks
The use of world-class bioinformatics facilities and human tumour samples on such a massive scale could result in methods of monitoring an individual’s cancer in more detail than ever before – creating impact on a truly global scale Prof. Tyler Jacks, Director of the Koch Institute MIT
Peter Rainey
This team's work could result in the development of important advanced techniques for surveillance and personalised risk analysis, which could provide early warnings of cancer-causing events. If the team's goals are realised, cancer incidence and mortality could be significantly reduced and it could be a major step forward in public health and prevention Peter Rainey, Grand Challenge Patient Advisory Panel

Can multiple myeloma help us determine what makes a cancer lethal?

On off switch
Dr Surinder Sahota (University of Southampton)
Dr Madhav Dhodapkar (Yale Cancer Center)
Dr Oscar Yanes (Universitat Rovira i Virgili)
Prof. Claire Edwards (University of Oxford)
Dr Jose Ignacio Martín-Subero (IDIBAPS)
Dr Dirk Hose (Heidelberg University)
Alan Chant

Summary:

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.

 

Dr Surinder Sahota
Our consortium is absolutely delighted at being shortlisted under the Cancer Research UK Grand Challenge call. Our response to the challenge of ‘distinguishing between lethal cancers that need treating and non-lethal cancers that don’t’ has only been made feasible by harnessing the available expertise worldwide Dr Surinder Sahota, University of Southampton
Dr Brian Duker
Understanding the evolution of fatal disease is one of the greatest challenges of our time. This application is taking the type of wide ranging approach necessary to tackle this challenge head on Dr Brian Druker, Director of OHSU
Margaret Grayson
This proposal, trying to find 'the switch point', could lead to thousands of lives being saved! Margaret Grayson, Grand Challenge Patient Advisory Panel

Lethal vs non-lethal prostate cancer: distinguishing the tigers from the pussycats

Prof. Freddie Hamdy (University of Oxford)
Dr David Wedge (Big Data Institute, University of Oxford)
Prof. Tapio Visakorpi (BioMediTech)
Dr Andrew Vickers (Memorial Sloan-Kettering Cancer Center)
Prof. Charles Swanton (Francis Crick Institute/University College London)
Prof. Ros Eeles (The Institute of Cancer Research)
Johann de Bono (The Institute of Cancer Research)
Prof. Colin Cooper (University of East Anglia)
Prof George Bova (Tampere University)
Not yet confirmed

Summary

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.

Prof. Freddie Hamdy
Prostate cancer is one of the most common, but also most controversial cancers to manage. We are now set to answer the most difficult question of all: How can we recognise aggressive disease as early as possible, in order to treat the right patient, at the right time, with the right treatment option? With this exciting world-leading team and unprecedented material from thousands of generous patients, we will rise to this challenge put to us by Cancer Research UK Prof. Freddie Hamdy, University of Oxford
Sir David Lane
This proposal is unique as it brings together a combination of techniques, disciplines and expertise which could only be funded together through a scheme like Grand Challenge. Its comprehensive approach from molecular level to clinical outcomes is exciting and makes patient benefit feel just around the corner Sir David Lane, Director A*Star
Terry Kavanagh
For years now, many of those unfortunate to have the disease have had to undergo radical invasive treatment that may not be necessary but this team’s ‘molecular checklist’ could help make this a thing of the past Terry Kavanagh, Grand Challenge Patient Advisory Panel

When is cancer not really cancer?

Dr Jelle Wesseling (Netherlands Cancer Institute)
Prof. Alastair Mark Thompson (MD Anderson Cancer Center)
Dr Serena Nik-Zainal (Wellcome Trust Sanger Institute)
Dr Shelley Hwang (Duke University School of Medicine)
Dr Phillip Andrew Futreal (MD Anderson Cancer Center)
Dr Jos Jonkers (Netherlands Cancer Institute)
Dr Adele Francis (University Hospitals Birmingham NHS Trust UK)
Maggie Wilcox, Ellen Verschuur, Liz Fernks and Deb Collyar

Summary:

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.

Dr Jelle Wesseling
We are delighted to be shortlisted to tackle a major health issue: distinguishing harmless from hazardous DCIS, a very common ‘pre-cancerous’ breast lesion. With the support of Cancer Research UK’s Grand Challenge, we will be privileged to have the expertise and the tools to revolutionize DCIS management, ultimately sparing many women with harmless DCIS unnecessary treatment, without compromising the excellent outcomes of DCIS management presently achieved Dr Jelle Wesseling, Netherlands Cancer Institute
Suzanne Cory
It’s the fresh thinking and drive to foster exceptional collaborations that excites me about this proposal and with clear clinical need, this global consortia could change the lives of patients worldwide. Professor Suzanne Cory, University of Melbourne
Terry Kavanagh
What a huge breakthrough this would be for those patients diagnosed with DCIS. To be able to accurately distinguish between lethal and non-lethal DCIS would spare those affected, from the emotional trauma of a diagnosis of breast cancer along with any unnecessary invasive treatment. Terry Kavanagh, Grand Challenge Patient Advisory Panel

Creating a 4D cancer atlas to track cancer’s journey

Prof. Ehud Shapiro (Weizmann Institute of Science)
Dr Ido Amit (Weizmann Institute of Science)
Prof. Caroline Dive (Cancer Research UK Manchester Institute)
Dr Levi Garraway (Dana-Farber Institute)
Dr John Marioni (Cancer Research UK Cambridge Institute)
Prof. Chris Ponting (University of Edinburgh)
Dr Aviv Regev (Broad Institute)
Prof. Charles Swanton (UCL Cancer Institute/Crick Institute)
Prof. Amos Tanay (Weizmann Institute of Science)
Dr Alexander van Oudenaarden (Hubrecht Institute)
Maggie Wilcox

Summary:

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

Professor Ehud Shapiro
The Cancer Research UK Grand Challenge call galvanized the pioneers of the emerging field of single-cell genomics. I am proud and excited to have these scientific leaders join me to apply our rapidly developing scientific discipline to finally provide a clear view, at single-cell resolution, of the creation and spread of metastases, the process that is the fundamental cause of cancer mortality Prof. Ehud Shapiro, Weizmann Institute of Science
Dr Rick Klausner
I am really excited about the in-situ, single cell imaging technology that could come from this project. The vital information it could provide would enable researchers to pin point the origin of tumours and track their spread revolutionising cancer treatment entirely Dr Rick Klausner, Chief Medical Officer at Illumina
Terry Kavanagh
I love this challenge. Tumour mapping; a personalised four dimensional atlas of cancer; a 3D mapping of a patients tumour; a 3D virtual reality scenario!! How ‘futuristic’ and exciting this proposal is. The fourth dimension 'time’ probably presents the biggest challenge Terry Kavanagh, Grand Challenge Patient Advisory Panel

Building a virtual reality interactive map of breast cancer

Prof. Greg Hannon (University of Cambridge)
Dr Nicholas Walton (University of Cambridge)
Dr Johanna Joyce (Ludwig Institute for Cancer Research)
Owen Harris (DEEP VR)
Prof. Edward S. Boyden (Massachusetts Institute of Technology)
Dr Samuel Aparicio (British Columbia Cancer Agency)
Prof. Shankar Balasubramanian (University of Cambridge)
Prof. Carlos Caldas (University of Cambridge)
Prof. Simon Tavaré (University of Cambridge)
Prof. Bernd Bodenmiller (University of Zurich)
Prof. Xiaowei Zhuang (Harvard University)
Lynn Dundas and Elaine Chapman

Summary:

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 ten 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.

Prof. Greg Hannon
We are delighted that Cancer Research UK might give us the opportunity building a fantastic international team to revolutionize the way we look at tumours. Possibilities to accomplish something on this scale are incredibly rare Prof. Greg Hannon, University of Cambridge
Prof. Nic Jones
The ambition and innovation shown in this proposal is what Grand Challenge is all about – creating a virtual reality experience of a tumour architecture could deliver a true paradigm shift in our approach to understanding how cancer develops and behaves Prof. Nic Jones, Cancer Research UK Chief Scientist Emeritus, Director CRUK Manchester Cancer Centre
Margaret Grayson
Imagine researchers and doctors being able to 'step inside' a tumour and watch what each cell is doing - for patients the impact on how we are diagnosed and treated in the future could be huge! Margaret Grayson, Grand Challenge Patient Advisory Panel

Charting unknown territory: mapping what we don’t know about a tumour

Dr Josephine Bunch (National Physical Laboratory)
Prof. Zoltan Takats (Imperial College London)
Dr Richard Goodwin (AstraZeneca)
Prof. Owen J. Sansom (Cancer Research UK Glasgow Institute)
Dr Mariia Yuneva (Francis Crick Institute)
Dr Heidi Goenaga Infante (LGC Ltd)
Dr George Poulogiannis (The Institute of Cancer Research)
Dr Ian Gilmore (National Physical Laboratory)
Maggie Brennan and Harry Hall

Summary:

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.

Dr Josephine Bunch
This opportunity would enable us to bring together developers of innovative imaging techniques with international experts in cancer metabolism for the first time. Together, we can start to unravel the mysteries behind the complex community of cancer cells living within a tumour and understand the chemistry of the infrastructure they rely on Dr Josephine Bunch, National Physical Laboratory
Prof. Ed Harlow
This cutting edge proposal brings together an impressive consortia uniting academia and pharma who will develop, and use, pioneering new imaging technology. The kind of detail they are proposing to capture could give us insight into the reorganisation of tumour cell networks at a level we have never seen before - opening up new worlds of possibility Prof. Ed Harlow, Harvard Medical School
Terry Kavanagh
Like any 'voyage of discovery’ charting unknown territory is bound to uncover a lot we don’t already know about cancer. It could lead to much needed technology that will identify new treatment targets for patients. Terry Kavanagh, Grand Challenge Patient Advisory Panel

Challenge 1 - Develop vaccines to prevent non-viral cancers

Eradicating cancer by vaccination against the tumour blood supply

Principal Investigator:
Prof. Roy Bicknell (University of Birmingham)
Co-Investigators:
Dr George Coukos (Ludwig Institute for Cancer Research) Prof. Arjan Griffioen (VU University Medical Centre) Dr Anna-Karin Olsson (Uppsala University) Dr Stephen Hodi (Dana-Farber Cancer Center/Broad Institute) Prof. Michele De Palma (Swiss Institute for Experimental Cancer Research) Prof. Gary W. Middleton (University of Birmingham) Prof. Douglas Hanahan (Swiss Institute for Experimental Cancer Research)
Patient Representative:
Jacqui Gath

Summary:

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.

Grand Challenge allows us, for the first time, to tackle the development of a universal cancer vaccine, something that would never be funded by other schemes as it would be deemed too difficult or high risk. It is this balance of accepting high risk elements to achieve great progress that makes Grand Challenge so exciting Prof. Roy Bicknell, University of Birmingham
I am excited about the approach of creating a vaccine that targets the tumour micro-environment as it could have huge clinical impact for many cancers. Novel strategies like this, turning traditional tactics on their heads, can make good science great Prof. Adrian Bird, University of Edinburgh
Jim Elliot
What is exciting about this proposal is that it is looking to combine both treatment and prevention as well as using the body's own defence mechanism, the immune system, to do this and so would potentially lead to a treatment that is both safe with little, if any, wider side effects and would be long lasting Jim Elliott, Grand Challenge Patient Advisory Panel

Challenge 2 - Eradicate EBV-induced cancers from the world

Ending EBV cancers

Principal Investigator:
Prof. Alan Rickinson (University of Birmingham)
Co-Investigators:
Dr Cliona Rooney (Baylor College of Medicine) Dr Steve Gottschalk (Baylor College of Medicine) Prof. Hans Clevers (Hubrecht Institute) Prof. Andreas Strasser (Walter and Eliza Hall Institute) Dr Paul Lieberman (Wistar Institute) Prof. Dr Ugur Sahin (TRON Translational Cancer Center) Dr Christian Munz (University of Zurich) Prof. Masashi Fukayama (University of Tokyo) Prof. Anthony Clan (Chinese University of Hong Kong) Dr Jeff Cohen (National Institutes of Health) Prof. Paul Lehner (University of Cambridge)
Patient Representative:
To be confirmed

Summary:

Grand Challenge Two 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.

Alan Rickinson
The Grand Challenge is a huge opportunity for our newly-assembled global team. Such support would take research on EBV to a new level and make possible the goal of eliminating the many cancers linked to this virus Professor Alan Rickinson, Birmingham University
Chris Wild
This team is ambitious and bold. Their integrated approach brings together a wide range of expertise and technology to take on the tough challenge of eradicating EBV induced cancer Dr Chris Wild, Director of IARC
Terry Kavanagh
I particularly welcome Professor Rickinson’s Challenge to develop a vaccine that can be used both as a treatment and a preventive measure for EBV. This research could also have a knock on effect giving support to the development of vaccines for other types of cancer Terry Kavanagh, Grand Challenge Patient Advisory Panel

Challenge 3 - Discover how unusual patterns of mutation are induced by different cancer-causing events

An early warning system for cancer: linking mutational signatures back to the events that caused them

Principal Investigator:
Prof. Sir Mike Stratton (Wellcome Trust Sanger Institute)
Co-Investigators:
Dr Paul Brennan ( IARC) Dr Ludmil Alexandrov (Los Alamos State Laboratory) Dr Allan Balmain (UCSF) Prof. Stephen Jackson (Wellcome Trust Sanger Institute) Prof. David Phillips (King's College London) Dr Peter Campbell (Wellcome Trust Sanger Institute)
Patient Representative:
Mimi McCord (Heartburn Cancer UK) and Maggie Blanks (Pancreatic Cancer Research Fund)

Summary:

There are big differences in cancer incidence between different parts of the world and the reasons for many of these remain unknown. Even where previous research suggests that complicated risk factors like obesity contribute, pinning down the mechanisms by which they cause cancer at a molecular level is challenging. Professor Mike Stratton’s team intend to address this on a grand and global scale.

To understand the geographical differences in cancer incidence they will study the DNA of thousands of cancers from carefully chosen locations around the world to uncover the “mutational signatures” left decades before by the environmental exposures and lifestyle practices responsible for the differences. They will combine this with lab-based research, building a comprehensive picture of the mutational signatures due to the hundreds of known and suspected human carcinogens, which they will then compare with those found in the cancers.

Their ultimate goal is to monitor these DNA signatures in healthy individuals to provide an early warning system that unsuspected exposures to cancer-causing agents have occurred, so that it might be possible to control the cancer risk before it has a chance to accumulate further.

Prof. Sir Mike Stratton
We’re thrilled to be shortlisted for Cancer Research UK’s Grand Challenge and to have been given the opportunity to bring together expertise in epidemiology and carcinogenesis complemented by Sanger’s large-scale genomics platforms. Cancer is a global problem and needs these large funding initiatives to deliver a step change in our understanding - an understanding which will allow us and others to develop new and better treatments and innovative, evidence-based prevention strategies. Prof. Sir Mike Stratton, Wellcome Trust Sanger Institute
Prof. Tyler Jacks
The use of world-class bioinformatics facilities and human tumour samples on such a massive scale could result in methods of monitoring an individual’s cancer in more detail than ever before – creating impact on a truly global scale Prof. Tyler Jacks, Director of the Koch Institute MIT
Peter Rainey
This team's work could result in the development of important advanced techniques for surveillance and personalised risk analysis, which could provide early warnings of cancer-causing events. If the team's goals are realised, cancer incidence and mortality could be significantly reduced and it could be a major step forward in public health and prevention Peter Rainey, Grand Challenge Patient Advisory Panel

Challenge 4 - Distinguish between lethal cancers that need treating, and non-lethal cancers that don’t

Can multiple myeloma help us determine what makes a cancer lethal?

Principal Investigator:
Dr Surinder Sahota (University of Southampton)
Co-Investigators:
Dr Madhav Dhodapkar (Yale Cancer Center) Dr Oscar Yanes (Universitat Rovira i Virgili) Prof. Claire Edwards (University of Oxford) Dr Jose Ignacio Martín-Subero (IDIBAPS) Dr Dirk Hose (Heidelberg University)
Patient Representative:
Alan Chant

Summary:

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.

 

Dr Surinder Sahota
Our consortium is absolutely delighted at being shortlisted under the Cancer Research UK Grand Challenge call. Our response to the challenge of ‘distinguishing between lethal cancers that need treating and non-lethal cancers that don’t’ has only been made feasible by harnessing the available expertise worldwide Dr Surinder Sahota, University of Southampton
Dr Brian Duker
Understanding the evolution of fatal disease is one of the greatest challenges of our time. This application is taking the type of wide ranging approach necessary to tackle this challenge head on Dr Brian Druker, Director of OHSU
Margaret Grayson
This proposal, trying to find 'the switch point', could lead to thousands of lives being saved! Margaret Grayson, Grand Challenge Patient Advisory Panel

Lethal vs non-lethal prostate cancer: distinguishing the tigers from the pussycats

Principal Investigator:
Prof. Freddie Hamdy (University of Oxford)
Co-Investigators:
Dr David Wedge (Big Data Institute, University of Oxford) Prof. Tapio Visakorpi (BioMediTech) Dr Andrew Vickers (Memorial Sloan-Kettering Cancer Center) Prof. Charles Swanton (Francis Crick Institute/University College London) Prof. Ros Eeles (The Institute of Cancer Research) Johann de Bono (The Institute of Cancer Research) Prof. Colin Cooper (University of East Anglia) Prof George Bova (Tampere University)
Patient Representative:
Not yet confirmed

Summary

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.

Prof. Freddie Hamdy
Prostate cancer is one of the most common, but also most controversial cancers to manage. We are now set to answer the most difficult question of all: How can we recognise aggressive disease as early as possible, in order to treat the right patient, at the right time, with the right treatment option? With this exciting world-leading team and unprecedented material from thousands of generous patients, we will rise to this challenge put to us by Cancer Research UK Prof. Freddie Hamdy, University of Oxford
Sir David Lane
This proposal is unique as it brings together a combination of techniques, disciplines and expertise which could only be funded together through a scheme like Grand Challenge. Its comprehensive approach from molecular level to clinical outcomes is exciting and makes patient benefit feel just around the corner Sir David Lane, Director A*Star
Terry Kavanagh
For years now, many of those unfortunate to have the disease have had to undergo radical invasive treatment that may not be necessary but this team’s ‘molecular checklist’ could help make this a thing of the past Terry Kavanagh, Grand Challenge Patient Advisory Panel

When is cancer not really cancer?

Principal Investigator:
Dr Jelle Wesseling (Netherlands Cancer Institute)
Co-Investigators:
Prof. Alastair Mark Thompson (MD Anderson Cancer Center) Dr Serena Nik-Zainal (Wellcome Trust Sanger Institute) Dr Shelley Hwang (Duke University School of Medicine) Dr Phillip Andrew Futreal (MD Anderson Cancer Center) Dr Jos Jonkers (Netherlands Cancer Institute) Dr Adele Francis (University Hospitals Birmingham NHS Trust UK)
Patient Representative:
Maggie Wilcox, Ellen Verschuur, Liz Fernks and Deb Collyar

Summary:

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.

Dr Jelle Wesseling
We are delighted to be shortlisted to tackle a major health issue: distinguishing harmless from hazardous DCIS, a very common ‘pre-cancerous’ breast lesion. With the support of Cancer Research UK’s Grand Challenge, we will be privileged to have the expertise and the tools to revolutionize DCIS management, ultimately sparing many women with harmless DCIS unnecessary treatment, without compromising the excellent outcomes of DCIS management presently achieved Dr Jelle Wesseling, Netherlands Cancer Institute
Suzanne Cory
It’s the fresh thinking and drive to foster exceptional collaborations that excites me about this proposal and with clear clinical need, this global consortia could change the lives of patients worldwide. Professor Suzanne Cory, University of Melbourne
Terry Kavanagh
What a huge breakthrough this would be for those patients diagnosed with DCIS. To be able to accurately distinguish between lethal and non-lethal DCIS would spare those affected, from the emotional trauma of a diagnosis of breast cancer along with any unnecessary invasive treatment. Terry Kavanagh, Grand Challenge Patient Advisory Panel

Challenge 5 - Find a way of mapping tumours at the molecular and cellular level

Building a virtual reality interactive map of breast cancer

Principal Investigator:
Prof. Greg Hannon (University of Cambridge)
Co-Investigators:
Dr Nicholas Walton (University of Cambridge) Dr Johanna Joyce (Ludwig Institute for Cancer Research) Owen Harris (DEEP VR) Prof. Edward S. Boyden (Massachusetts Institute of Technology) Dr Samuel Aparicio (British Columbia Cancer Agency) Prof. Shankar Balasubramanian (University of Cambridge) Prof. Carlos Caldas (University of Cambridge) Prof. Simon Tavaré (University of Cambridge) Prof. Bernd Bodenmiller (University of Zurich) Prof. Xiaowei Zhuang (Harvard University)
Patient Representative:
Lynn Dundas and Elaine Chapman

Summary:

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 ten 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.

Prof. Greg Hannon
We are delighted that Cancer Research UK might give us the opportunity building a fantastic international team to revolutionize the way we look at tumours. Possibilities to accomplish something on this scale are incredibly rare Prof. Greg Hannon, University of Cambridge
Prof. Nic Jones
The ambition and innovation shown in this proposal is what Grand Challenge is all about – creating a virtual reality experience of a tumour architecture could deliver a true paradigm shift in our approach to understanding how cancer develops and behaves Prof. Nic Jones, Cancer Research UK Chief Scientist Emeritus, Director CRUK Manchester Cancer Centre
Margaret Grayson
Imagine researchers and doctors being able to 'step inside' a tumour and watch what each cell is doing - for patients the impact on how we are diagnosed and treated in the future could be huge! Margaret Grayson, Grand Challenge Patient Advisory Panel

Charting unknown territory: mapping what we don’t know about a tumour

Principal Investigator:
Dr Josephine Bunch (National Physical Laboratory)
Co-Investigators:
Prof. Zoltan Takats (Imperial College London) Dr Richard Goodwin (AstraZeneca) Prof. Owen J. Sansom (Cancer Research UK Glasgow Institute) Dr Mariia Yuneva (Francis Crick Institute) Dr Heidi Goenaga Infante (LGC Ltd) Dr George Poulogiannis (The Institute of Cancer Research) Dr Ian Gilmore (National Physical Laboratory)
Patient Representative:
Maggie Brennan and Harry Hall

Summary:

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.

Dr Josephine Bunch
This opportunity would enable us to bring together developers of innovative imaging techniques with international experts in cancer metabolism for the first time. Together, we can start to unravel the mysteries behind the complex community of cancer cells living within a tumour and understand the chemistry of the infrastructure they rely on Dr Josephine Bunch, National Physical Laboratory
Prof. Ed Harlow
This cutting edge proposal brings together an impressive consortia uniting academia and pharma who will develop, and use, pioneering new imaging technology. The kind of detail they are proposing to capture could give us insight into the reorganisation of tumour cell networks at a level we have never seen before - opening up new worlds of possibility Prof. Ed Harlow, Harvard Medical School
Terry Kavanagh
Like any 'voyage of discovery’ charting unknown territory is bound to uncover a lot we don’t already know about cancer. It could lead to much needed technology that will identify new treatment targets for patients. Terry Kavanagh, Grand Challenge Patient Advisory Panel

Creating a 4D cancer atlas to track cancer’s journey

Principal Investigator:
Prof. Ehud Shapiro (Weizmann Institute of Science)
Co-Investigators:
Dr Ido Amit (Weizmann Institute of Science) Prof. Caroline Dive (Cancer Research UK Manchester Institute) Dr Levi Garraway (Dana-Farber Institute) Dr John Marioni (Cancer Research UK Cambridge Institute) Prof. Chris Ponting (University of Edinburgh) Dr Aviv Regev (Broad Institute) Prof. Charles Swanton (UCL Cancer Institute/Crick Institute) Prof. Amos Tanay (Weizmann Institute of Science) Dr Alexander van Oudenaarden (Hubrecht Institute)
Patient Representative:
Maggie Wilcox

Summary:

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

Professor Ehud Shapiro
The Cancer Research UK Grand Challenge call galvanized the pioneers of the emerging field of single-cell genomics. I am proud and excited to have these scientific leaders join me to apply our rapidly developing scientific discipline to finally provide a clear view, at single-cell resolution, of the creation and spread of metastases, the process that is the fundamental cause of cancer mortality Prof. Ehud Shapiro, Weizmann Institute of Science
Dr Rick Klausner
I am really excited about the in-situ, single cell imaging technology that could come from this project. The vital information it could provide would enable researchers to pin point the origin of tumours and track their spread revolutionising cancer treatment entirely Dr Rick Klausner, Chief Medical Officer at Illumina
Terry Kavanagh
I love this challenge. Tumour mapping; a personalised four dimensional atlas of cancer; a 3D mapping of a patients tumour; a 3D virtual reality scenario!! How ‘futuristic’ and exciting this proposal is. The fourth dimension 'time’ probably presents the biggest challenge Terry Kavanagh, Grand Challenge Patient Advisory Panel

 

 

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