PROSPECT
Determine why the incidence of early-onset cancers in adults is rising globally
Dr Yin Cao, Co-team Lead
Associate Professor of Surgery & Medicine
Washington University in St. Louis
Professor Andrew Chan, Co-team Lead
Daniel K. Podolsky Professor of Medicine
Massachusetts General Hospital
INSTITUTIONS
9
LOCATIONS
France, India, Italy, UK, US
FUNDED BY
Cancer Research UK, National Cancer Institute, the Bowelbabe Fund for Cancer Research UK, Institut National Du Cancer (INCa)
SPECIALISMS
biochemistry, cancer biology, clinical and global oncology, computational biology, epidemiology, epigenomics, gastroenterology, immunology, microbiome, nutrition, pathology
Pathways, risk factors and molecules to prevent early-onset colorectal tumours
Funded by:
Team PROSPECT will employ a disruptive, transdisciplinary approach spanning cells, individuals and populations to uncover the mechanisms linking lifetime exposures to early-onset colorectal cancer, and test new strategies to combat this cancer type.
Although recent decades have seen a decrease in the overall incidence of colorectal cancer, there has been an alarming rise in the number of cases diagnosed in people under 50 years of age (early-onset colorectal cancer [EOCRC]) in multiple countries across the world. Research suggests that this risk is increasing with each new generation and is likely linked to exposures in early life and throughout an individual’s lifetime that are specific to their birth cohort.
Although progress has been made in understanding some of the factors associated with increased risk of EOCRC, such as obesity, sedentary behaviours and poor diet, many unanswered questions remain about the mechanisms responsible for the rise in cases.
Team PROSPECT aims to address the global rise in the incidence of EOCRC by understanding the pathways, risk factors and molecules involved in its development. The team’s collective vision is to understand and ultimately reverse the network of causal factors throughout the life course that disrupts biological homeostasis to promote EOCRC.
Tackling the Early-onset cancers challenge
The team has three overarching objectives for tackling this challenge:
Identify the risk factors associated with EOCRC
To identify the risk factors that contribute to the rising incidence of EOCRC, the team will leverage prospective data from more than 15 diverse human cohorts from across the UK, US, multiple countries in Europe, and Mexico, encompassing over 2,700 EOCRC cases.
The team will look at exposure to known risk factors (such as obesity and poor diet) and novel risk factors (including environmental and social factors), as well as features of the microbiome that could contribute to EOCRC. These exposures are collectively known as the exposome.
Characterise the underlying mechanisms of causal risk factors
The population data the team collects will feed into research to understand how the identified risk factors cause biological changes that increase susceptibility to, or drive the progression of, EOCRC. Insights and hypotheses from human data will be tested in innovative animal models and in vitro organoid models.
Integrating population-based and experimental studies, the team hopes to identify at which life stage the risk factors begin to play a role in the development of EOCRC.
Develop precision prevention strategies
PROSPECT’s ultimate goal is to identify ways to prevent the development of EOCRC. The team will set up two types of trials: precision prevention trials (in the US and UK) to explore if treating young adults with an increased risk of EOCRC with anti-obesity drugs or dietary interventions can interfere with the molecular pathways linked with increased risk; and community risk assessment trials (in the UK and India) to determine whether knowing EOCRC risk influences people’s motivation to adapt their lifestyles or undergo screening to reduce or prevent this risk.
From identifying the causes and mechanisms of EOCRC to developing clinical trials and interventions to reduce the burden of this cancer type, PROSPECT’s goal is to shape a hopeful and healthier future for younger generations. The team’s patient advocates will ensure that its studies are inclusive and address the needs of diverse communities.
Professor Andrew Chan, Co-team Lead
Daniel K. Podolsky Professor of Medicine
The alarming rise of colorectal cancer in young people around the world demands immediate action. Only by pushing the boundaries of our individual fields can we move quickly to identify opportunities for preventive interventions that can benefit younger generations.
Plain language summary
More and more people under 50 years of age are being diagnosed with bowel (or colorectal) cancer in at least 18 countries around the world. These cases are called early-onset colorectal cancer (EOCRC), and each new generation faces higher risks of developing this cancer type.
Research has uncovered a few drivers of this alarming trend, including obesity and poor diet. However, prior studies usually assessed the impact of these factors at a single time point in adulthood. There remains a pressing need to further the understanding of existing risk factors throughout an individual’s lifetime, as well as to identify new risk factors.
Team PROSPECT will study factors contributing to EOCRC by analysing samples from diverse populations worldwide. They will look at known risk factors (such as obesity and poor diet) and new risk factors (including environmental and social factors). In laboratory experiments, they’ll investigate how these factors lead to cell changes linked to EOCRC.
By understanding the complex network of risk factors that lead to EOCRC, PROSPECT aims to develop new methods to assess risk and prevent colorectal cancer in individuals under 50 years of age. The team will test these methods in trials in the clinic and in communities.
Dr Yin Cao, ScD, MPH is a molecular cancer epidemiologist and Associate Professor of Surgery and Medicine at Washington University in St Louis and Alvin J. Siteman Cancer Center. Her lab applies rigorous epidemiologic methods and leverages large cohorts, genetic consortia, real-world evidence, and high-throughput technologies to investigate the etiology and risk factors throughout the life course for early-onset cancers. Her work led the field of early-onset colorectal cancer by uncovering risk factors that may contribute to the rising incidence, such as obesity, diabetes, metabolic comorbid conditions, prolonged sitting, poor diet, sugar sweetened beverages, alcohol drinking pattern, and birth via cesarean delivery. Her team also focuses on prominent issues in the early detection and survivorship of early-onset cancers. Besides etiologic research, she is also committed to bridging the gap between evidence and implementation, through advancing the integration of epidemiologic evidence with microsimulation modeling.
Yin’s work has been recognized by the National Comprehensive Cancer Network (NCCN) Young Investigator Award, American Gastroenterological Association (AGA) Young Investigator Award in Clinical Science, 40 Under 40 in Cancer Award, and National Cancer Institute MERIT award. She serves as an Associate Editor for the Journal of National Cancer Institute.
Organisation
Washington University
Andrew T. Chan, MD, MPH is a physician-scientist at Massachusetts General Hospital (MGH) known for his work in cancer prevention, with a focus on the role of pharmacologic preventives, diet, and the gut microbiome in cancer. As a practicing gastroenterologist and molecular epidemiologist, he has pioneered precision prevention approaches through translational research which spans population cohorts to clinical trials.
Professor Chan is the Daniel K. Podolsky Professor of Medicine at Harvard Medical School and Professor of Immunology and Infectious Diseases at Harvard T. H. Chan School of Public Health. He holds leadership roles at MGH, including Chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital and Director of Epidemiology at the MGH Cancer Center. He is co-leader of the Cancer Epidemiology Program of the Dana-Farber Harvard Cancer Center.
Among his honors, Professor Chan is an American Cancer Society Research Professor, an Outstanding Investigator of the U.S. National Cancer Institute (NCI), and an elected member of the American Society for Clinical Investigation and the Association of American Physicians. He serves on the NCI Director’s Board of Scientific Advisors, the Governing Board of the American Gastroenterological Association, the Population Sciences Working Group of the American Association for Cancer Research as past chair, and the Health Equity Committee of Stand Up to Cancer.
Organisation
Massachusetts General Hospital
Professor Emily Balskus is a chemical biologist whose research focuses on deciphering microbial metabolism and its role in complex ecosystems like the human gut microbiome. Using chemical knowledge and tools, she discovers new microbial enzymes and metabolites with the ultimate goal of elucidating their impacts on host biology and the microbiome. Emily and her group are known for their contribution to elucidating the structure and mode of action of the DNA damaging gut bacterial genotoxin colibactin, which is linked to colorectal cancer, as well as their work uncovering additional gut microbial metabolic processes that influence host responses to dietary components and medicines.
Emily is currently the Thomas Dudley Cabot Professor of Chemistry at Harvard University and a Howard Hughes Medical Institute Investigator. Her Her research has been recognized with multiple awards, including the 2019 Blavatnik Award for Young Scientists in Chemistry and the 2020 Alan T. Waterman Award.
Organisation
Harvard University
Professor Yasmine Belkaid is an immunologist and the President of the Pasteur Institut. Previously, she was a Distinguished Investigator at the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH), and led the Laboratory of Host Immunity and Microbiome at NIH. Her lab aims to understand the tissue-specific regulatory responses to infection throughout the life course and mechanisms by which host-microbial responses are regulated in tissues, including the intestine and how dysregulation of these responses leads to pathology.
Professor Belkaid has published more than 220 scientific papers on infection, immunity, immunology, microbiota and nutrition. She has received numerous awards and honors, including the Robert Koch Prize (2021), the Lurie Prize in Biomedical Sciences (2019) and the Sanofi-Institut Pasteur Prize (2016). She is a member of several scientific committees and advisory boards, including the American Academy of Arts and Sciences, the National Academy of Medicine, and the National Academy of Sciences, as well as the Microbiome Technical Advisory Group at the Bill & Melinda Gates Foundation, the NIH Anti-Racism Steering Committee, the American Society of Microbiology and the Genentech Scientific Resource Board.
Organisation
Institut Pasteur
Jason Buenrostro is an Associate Professor at Harvard University in the department of Stem Cell and Regenerative Biology and co-Director of the Gene Regulation Observatory at the Broad Institute. Dr. Buenrostro is developing new technologies and computational tools to map the activity of gene regulatory elements, define their interactions, and build models that reveal regulatory circuits within cells. Using these mechanistic maps of gene regulation, Dr. Buenrostro looks to understand how cells acquire and reverse epigenetic changes and how these changes lead to disease.
Organisation
Harvard University
Curtis Huttenhower, PhD, is a Professor of Computational Biology and Bioinformatics in the Departments of Biostatistics and Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health, where he co-directs the Harvard Chan Microbiome in Public Health Center. He is an Associate Member at the Broad Institute's Microbiome Program. His lab focuses on computational methods for functional analysis of microbial communities and molecular epidemiology of the human microbiome. This includes systems biology reconstructions integrating metagenomic, metatranscriptomic, and other microbial community 'omics, microbiome ecology in health and disease, and its potential as a diagnostic tool and point of therapeutic intervention.
Organisation
Broad Institute
Professor Gary Patti is a pioneer of mass spectrometry-based technologies to perform metabolomics, lipidomics, and chemical exposomics at the population level with high throughput. He has contributed to the development of key computational resources that are widely used by scientists around the world, and he currently leads the NIH Omics Production Center. By applying these technologies to cancer, Professor Patti has elucidated mechanisms underlying the Warburg effect and previously unrecognized pathways for the utilization of lactate, fatty acids, fructose, and other dietary nutrients.
Dr. Patti is the Michael and Tana Powell Professor at Washington University in St. Louis, where he holds appointments in the departments of chemistry, genetics, and medicine. Professor Patti is the Senior Director of the Center for Mass Spectrometry and Metabolic Tracing, Director of the Clinical Science Research Core, Co-Director of the Metabolomics Core at the Siteman Cancer Center, Dean's Fellow of Advancement and Entrepreneurship, Director of Faculty Affairs, and the Chief Scientific Officer and Co-Founder of Panome Bio.
Professor Patti has been recognized with numerous awards including the Pew Scholars Award, the Camille Dreyfus Award, the Mallinckrodt Scholar Award, the American Chemical Society Midwest Award, and the inaugural NIEHS Award for revolutionizing innovative, visionary environmental health research.
Organisation
Washington University
Professor Nicola Segata is a Principal Investigator at the CIBIO Department of the University of Trento (Italy) and the European Institute of Oncology in Milan (Italy). As a computational biologist, Nicola has a background in metagenomics, machine learning, microbiome research, and microbial genomics. In 2012, Nicola completed a postdoctoral experience in Curtis Huttenhower Lab at Harvard (USA) where he was involved in the NIH Human Microbiome Project. In 2013, Nicola founded the Laboratory of Computational Metagenomics that has been bringing together computational scientists, experimental biologists, statisticians, and clinicians to study the diversity of the human microbiome and its role in human diseases. The Laboratory research efforts are directed toward exploration of microbiomes with strain-level resolution and meta-analysis of very large sets of metagenomes with novel computational approaches.
Organisation
University of Trento
Dr Sirohi is the Medical Director at BALCO Medical Centre, Raipur and a Breast /GI cancers Medical Oncologist. She has more than two decades of experience as an oncologist in UK & India. Having qualified as an oncologist from Tata Memorial Centre, Mumbai, she further completed her training at Royal Marsden NHS Foundation Trust, UK. She has published more than 200 papers in national and international journals and has lectured worldwide. She has been involved in varied capacities to create cancer awareness in India be it through cancer screening camps in various states to the initial setting up of cancer centers in the private or public sector to enabling protocols and procedures for safe care of patients. She is on the Lancet Oncology international advisory board. Her research and education interests center around cancer control in India. She sits on the ASCO committee for health equity and outcomes; & climate change and cancer. She has been part of the steering group of the “Cancer Control in Low- and Middle- Income Countries” conference held annually at the Royal Society of Medicine, London
Organisation
BALCO Medical Centre
Tim Spector is a medically qualified Professor of Epidemiology and Director of the TwinsUK Registry at King’s College London. His current work focuses on the microbiome and nutrition, and he is co-founder of ZOE, a personalised nutrition company, which runs the world’s largest nutrition study, ZOE Predict and has created a commercial at-home kit for personalised nutrition. He is also the lead researcher behind the world's biggest citizen science health project - the ZOE Health Study, formerly known as ZOE COVID Study, which provided essential data in response to the pandemic. He was awarded an OBE for this work. Having published more than 900 research articles, he is ranked in the top 100 of the world’s most cited scientists by Google. He is the author of four popular science books, including "The Diet Myth”, "Spoon Fed", and most recently “Food for Life”, a Sunday Times bestseller. He makes regular appearances on social and mainstream media.
Organisation
King’s College London
Ömer Yilmaz is the Eisen and Chang Career Development Associate Professor of Biology at the Koch Institute for Integrative Cancer Research at MIT and a gastrointestinal pathologist at the Massachusetts General Hospital and Harvard Medical School. Since it’s inception, the Yilmaz lab has been known for the work understanding how intestinal stem cells and their microenvironment adapt to diverse diets in the context of tissue regeneration, aging, and cancer initiation and progression. Since ISCs, like all adult stem cells, possess the ability to self-renew and the capacity for differentiating into tissue-specific cell types, they likely play an important role in remodeling the intestine in response to diet-induced physiologies. In addition, his lab has developed numerous tools and techniques to better model colon cancer using murine and patient-derived tissues. His achievements, to date, have been recognized with a Harold Weintraub Award (2007), a V Scholar Award (2015), a Pew-Stewart Trust Fellowship (2016), a Sidney Kimmel Fellowship (2016), a Sabri Ulker International Science Prize (2018), and a AAAS Martin and Rose Wachtel Cancer Research Prize (2018).
Organisation
Massachusetts Institute of Technology
Dr. Anisha Patel (MBchB, MRCP, DFSRH, DRCOG, MRCGP) is a stage IIIB rectal cancer survivor and a GP (family doctor). She is also a media doctor, keynote speaker and panelist, bowel cancer campaigner, health educator and author of the Amazon bestseller “Everything you’d hoped you’d never need to know about bowel cancer”.
Since Anisha’s cancer diagnosis, she has been driven to use her unique experiences as both a doctor and a patient in helping others navigate their patient journey, educating health professionals and the general public. Anisha is often found discussing bowel cancer in the public eye through various media outlets, and through social media @ doctorsgetcancertoo working to break down barriers, educate and inform the public, and encouraging cancer screening uptake especially in those communities with the lowest uptake. She has been involved in numerous cancer campaigns alongside charities, with the NHS and on screen, disseminating public health messages.
Anisha works for a number of charities voluntarily (including CRUK, Bowel cancer UK, Macmillan), as a media volunteer, an advisor and as a supporter. Anisha also is a friend of the Bowelbabefund Anisha has been appointed as a beneficiary Trustee for Teens Unite, an organisation supporting teens and young adults diagnosed with cancer through treatment and living with and beyond cancer. She is also Patron of the Fountain centre charity, where her and her family received holistic treatment and therapy during and after her cancer treatment.
She has also been involved in helping engage and recruit individuals into the UK’s biggest research project, Our Future Health, to ensure representation as well. She also had meetings at the governmental level to discuss healthcare and cancer policies.