Review

. 2018 Jan;67(1):179-193.

doi: 10.1136/gutjnl-2017-315333.

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

Mark Lawler¹, Deborah Alsina², Richard A Adams³, Annie S Anderson⁴, Gina Brown⁵, Nicola S Fearnhead⁶, Stephen W Fenwick⁷, Stephen P Halloran⁸, Daniel Hochhauser⁹, Mark A Hull¹⁰, Viktor H Koelzer¹¹, Angus G K McNair¹², Kevin J Monahan¹³, Inke Näthke¹⁴, Christine Norton¹⁵, Marco R Novelli¹⁶, Robert J C Steele⁴, Anne L Thomas¹⁷, Lisa M Wilde^{2

18}, Richard H Wilson¹, Ian Tomlinson¹⁹; Bowel Cancer UK Critical Research Gaps in Colorectal Cancer Initiative

Collaborators, Affiliations

Collaborators

Bowel Cancer UK Critical Research Gaps in Colorectal Cancer Initiative:
Sam H Ahmedzai, Jervoise Andreyev, Nicholas Arbuthnot, Wendy Atkin, Simon Bach, Lindy Berkman, Nicola Bloor, Victor Boulter, David Brewster, Karen Brown, John Burn, Jean-Baptiste Cazier, Ian Chau, Jeremy Cheadle, Ann Cole, Vicky Coyle, David Cunningham, Mark Davies, Julian Downward, Malcom Dunlop, Callum Fraser, Marco Gerlinger, Adam Glaser, Vicky Goh, David González De Castro, Trevor Graham, John Griffith, Steve Halligan, Willie Hamilton, Julie Hepburn, Rachel Haynes, Joe Higgins, Georgina Hold, Georgy Holden, Richard Houlston, Gill Hubbard, Tariq Iqba, Alexandra E Irvine, Tim Iveson, Nick Jakowiw, Ian Jackson, Monica Jefford, Dan Longley, Ultan Mcdermott, Michael Machesney, Jane Maher, Julian Marchesi, Tim Maughan, Gary Middleton, Barbara Moss, Mark Moss, Peter Murchie, Peter O'sullivan, Clint Robertson, Matt Rutter, Leslie Samuel, Owen Sansom, John Saxton, Ed Seward, Ricky Sharma, Tracy Smith, Andrea Sottoriva, Will Steward, Phil Stocker, Gillian Sweetman, Christian Von Wagner, Ann Williams, Doug Winton

Affiliations

¹ Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
² Bowel Cancer UK, London, UK.
³ School of Medicine, Cardiff University, Cardiff, UK.
⁴ Research into Cancer Prevention and Screening, University of Dundee, Dundee, UK.
⁵ Department of Radiology, Royal Marsden Hospital, Sutton, UK.
⁶ Department of Colorectal Surgery, Addenbrooke's Hospital, Cambridge, UK.
⁷ Hepatobiliary Surgery Unit, Aintree University Hospital, Liverpool, UK.
⁸ Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
⁹ Department of Oncology, University College London Cancer Institute, London, UK.
¹⁰ Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.
¹¹ Molecular and Population Genetics Laboratory, University of Oxford, Oxford, UK.
¹² Centre for Surgical Research, University of Bristol, Bristol, UK.
¹³ Family History of Bowel Cancer Clinic, Imperial College London, London, UK.
¹⁴ School of Life Sciences, University of Dundee, Dundee, UK.
¹⁵ Florence Nightingale Faculty of Nursing and Midwifery, King's College London, London, UK.
¹⁶ Research Department of Pathology, University College London Medical School, London, UK.
¹⁷ Leicester Cancer Research Centre, University of Leicester, Leicester, UK.
¹⁸ Atticus Consultants Ltd, Croydon, UK.
¹⁹ Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

PMID: 29233930
PMCID: PMC5754857
DOI: 10.1136/gutjnl-2017-315333

Review

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

Mark Lawler et al. Gut. 2018 Jan.

. 2018 Jan;67(1):179-193.

doi: 10.1136/gutjnl-2017-315333.

Authors

Collaborators

Bowel Cancer UK Critical Research Gaps in Colorectal Cancer Initiative:
Sam H Ahmedzai, Jervoise Andreyev, Nicholas Arbuthnot, Wendy Atkin, Simon Bach, Lindy Berkman, Nicola Bloor, Victor Boulter, David Brewster, Karen Brown, John Burn, Jean-Baptiste Cazier, Ian Chau, Jeremy Cheadle, Ann Cole, Vicky Coyle, David Cunningham, Mark Davies, Julian Downward, Malcom Dunlop, Callum Fraser, Marco Gerlinger, Adam Glaser, Vicky Goh, David González De Castro, Trevor Graham, John Griffith, Steve Halligan, Willie Hamilton, Julie Hepburn, Rachel Haynes, Joe Higgins, Georgina Hold, Georgy Holden, Richard Houlston, Gill Hubbard, Tariq Iqba, Alexandra E Irvine, Tim Iveson, Nick Jakowiw, Ian Jackson, Monica Jefford, Dan Longley, Ultan Mcdermott, Michael Machesney, Jane Maher, Julian Marchesi, Tim Maughan, Gary Middleton, Barbara Moss, Mark Moss, Peter Murchie, Peter O'sullivan, Clint Robertson, Matt Rutter, Leslie Samuel, Owen Sansom, John Saxton, Ed Seward, Ricky Sharma, Tracy Smith, Andrea Sottoriva, Will Steward, Phil Stocker, Gillian Sweetman, Christian Von Wagner, Ann Williams, Doug Winton

Affiliations

¹ Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
² Bowel Cancer UK, London, UK.
³ School of Medicine, Cardiff University, Cardiff, UK.
⁴ Research into Cancer Prevention and Screening, University of Dundee, Dundee, UK.
⁵ Department of Radiology, Royal Marsden Hospital, Sutton, UK.
⁶ Department of Colorectal Surgery, Addenbrooke's Hospital, Cambridge, UK.
⁷ Hepatobiliary Surgery Unit, Aintree University Hospital, Liverpool, UK.
⁸ Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.
⁹ Department of Oncology, University College London Cancer Institute, London, UK.
¹⁰ Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.
¹¹ Molecular and Population Genetics Laboratory, University of Oxford, Oxford, UK.
¹² Centre for Surgical Research, University of Bristol, Bristol, UK.
¹³ Family History of Bowel Cancer Clinic, Imperial College London, London, UK.
¹⁴ School of Life Sciences, University of Dundee, Dundee, UK.
¹⁵ Florence Nightingale Faculty of Nursing and Midwifery, King's College London, London, UK.
¹⁶ Research Department of Pathology, University College London Medical School, London, UK.
¹⁷ Leicester Cancer Research Centre, University of Leicester, Leicester, UK.
¹⁸ Atticus Consultants Ltd, Croydon, UK.
¹⁹ Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.

PMID: 29233930
PMCID: PMC5754857
DOI: 10.1136/gutjnl-2017-315333

Abstract

Objective: Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes.

Design: RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants.

Results: Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders.

Conclusion: Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years.

Keywords: colorectal cancer.

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Conflict of interest statement

Competing interests: ML reports support from Pfizer, outside the submitted work; DA reports grants from the Norman Foster Foundation, grants from the Tom Simms Memorial Fund at Queen’s University Belfast, during the conduct of the study; Dr Andreyev reports other from Entrinsic Health Solutions, Inc and personal fees from Macmillan Cancer Support, outside the submitted work; Professor Atkin reports grants from Cancer Research UK, outside the submitted work; Mr Bach reports personal fees from Ethicon Inc, outside the submitted work; Professor Burn has a patent A novel panel of short coding repeats suitable for high-throughput detection of microsatellite instability pending to Newcastle University; Dr Chau reports grants from Eli-Lily, Janssen-Cilag, Sanofi Oncology, Merck-Serono, and Novartis, personal fees from Taiho, Pfizer, Amgen, Eli-Lily, outside the submitted work; Professor Cheadle has a patent MUTYH gene variants licensed to Myriad Genetics and receives royalties; Professor Cunningham reports grants from Amgen, AstraZeneca, Bayer, Celgene, Medimmune, Merck Serono, Merrimack, and Sanofi, outside the submitted work; Professor Fraser reports personal fees from Immunostics Inc, Ocean, NJ, USA, Kyowa, Tokyo, Japan, and support for travel from Alpha Labs Ltd, Eastleigh, Hants, UK, during the conduct of the study; DH reports MRC CASE Award with Merck Serono for project unrelated to this submission and research support from Merck Serono for project unrelated to this submission; MH reports other from consultancy for Thetis Pharma, outside the submitted work; CN reports personal fees from Takeda and Ferring, outside the submitted work; Dr Sharma reports grants, personal fees and other from Sirtex, grants, personal fees and other from BTG, during the conduct of the study; AT reports personal fees from BMS Advisory Board, Roche Speaker Panel, Amgen Advisory Board, and Servier Advisory Board, outside the submitted work; LMW reports personal fees from Atticus Consultants Ltd, during the conduct of the study; RW reports personal fees from BMS Advisory Board, Clovis Oncology Advisory Board, Halozyme Advisory Board, Amgen Advisory Board, Servier Advisory Board, and Sirtex Independent Data Monitoring and Safety Committee, all outside the submitted work. RA, Professor Ahmedzai, ASA, Mr Arbuthnot, Mrs Berkman, Miss Bloor, Mr Boulter, Mrs Cole, Dr Brewster, GB, Professor Cazier, Dr Coyle, Mr Davies, Professor Downward, Professor Dunlop, NSF, SF, Dr Gerlinger, Dr Glaser, Professor Goh, Professor González De Castro, Dr Graham, Mr Griffith, Professor Halligan, SPH, Professor Hamilton, Mrs Hepburn, Dr Hold, Mr Holden, Professor Houlston, Dr Hubbard, Dr Iqbal, Dr Irvine, Dr Iveson, Mr Jackson, Mr Jakowiw, Mrs Jefford, Professor Longley, Dr McDermott, AGKM, Mr Machesney, Professor Maher, Professor Marchesi, Professor Maughan, Professor Middleton, Mr Moss, Mrs Moss, KJM, Dr Murchie, IN, MRN, Mr O’Sullivan, Mr Robertson, Professor Rutter, Dr Sansom, Dr Samuel, Professor Saxton, Dr Seward, Mrs Smith, Dr Sottoriva, RS, Professor Steward, Mr Stocker, Mrs Sweetman, IT, Dr Von Wagner and Professor Williams have nothing to disclose.

Figures

**Figure 1**
Bowel Cancer UK Critical Research Gaps in Colorectal Cancer Initiative process.

See this image and copyright information in PMC

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Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

Collaborators

Affiliations

Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases