The OPTIMISTICC Patient Advocate team is a diverse group from North American and Europe, with a wide range of backgrounds, professions, and interests. The one thing that we all have in common is a very personal link to colorectal cancer. Most of us are survivors, and we include within our number some Stage 4 survivors. We are united in our commitment to trying to identify the cause of this cancer, to eliminate the disease, and to take the luck out of existing diagnoses and treatments.
Every Patient Advocate is aligned with and embedded into one of the OPTIMISTICC research work packages. Our specific contribution is to ensure that research being undertaken focuses on the benefit it may bring to those who may be diagnosed with bowel cancer in the future.
About the Program
The information below provides a high level overview of the OPTIMISTICC grant and research.
Click each Work Package (WP) to see its overview, slides, and team members.
Our grant addresses the gut microbiome which consists of microorganisms including bacteria, fungi, and viruses. Together, they form a community called the microbiota or microbiome, which differs from organ to organ and person to person. Scientists have shown that these microorganisms have important roles in maintaining human health, but they can also play a role in the development of disease – including cancer.
To meet this Grand Challenge, we are focusing on two parts. The first part is an atlas of the colorectal cancer microbiome, across time and space. The goal is to understand how genetics and lifestyle risks impact the development of the colon cancer microbiome, and how this microbiome varies in populations. We will also examine the location of the microbiome within the colon cancer—how the microbiome is connected to cancer, immune and other human cells.
The second part is to investigate what happens when we try to treat the microbiome. Here the interactions between the microbiome and the immune system will be studied, and we will assess how current colon cancer treatments affect the microbiome. We will also analyze innovative new treatments that either treat the colon cancer microbiome or replace it with a healthier microbiome.
We have assembled a unique international team of physicians, scientists, and patient advocates to address these important and challenging questions in six separate work packages. The members of our team have led the way in understanding the biology of colon cancer, in general, and the colon cancer microbiome. We believe that we are the right group, at the right time, to address these important questions.
Researchers from our team have discovered that unique populations of bacteria not found in the normal colon are present in colorectal cancers and pre cancers. These bacteria, also known as the colorectal cancer microbiota or microbiome, are found in cancers within the colon and in colon cancers that have spread, or metastasized, to other organs.
By the end of the project, we hope to have a greater understanding of the microbiota’s relationship and impact on the risk, diagnosis and spread of colorectal cancer. We also hope to identify novel treatment strategies by manipulating the microbiota, and to gain insight into the impact of the microbiota on treatment and survivorship in people with colorectal cancer.
We are analyzing the microbiome of 3000 bowel tumors, to determine the relationship between the bacteria within tumors and their mutations. We have analyzed the microbiome of over 2288 bowel cancer screening samples. Our results suggest that the microbiome can improve screening accuracy. We are now successfully collecting samples from Chile, Argentina, India, and Vietnam and have demonstrated that transportation does not adversely affect it. We have found commonality of the bacteria in the microbiome of people with bowel tumors irrespective of country of origin. We are recruiting 500 individuals with hereditary colon cancer to collect stool and general information about risk factors. We are conducting a study of 2500 patients currently undergoing a screening colonoscopy to define the relationship between mucosal bacteria and fecal bacteria. We have a variety of mouse models to test the effect of specific bacteria or communities of bacteria on the formation of colon tumors.
Work Package Leaders
Philip Quirke, BM, PhD, FRCPath, FRCSEd (ad hominem), FFPath (Hon), RCPI, FMedSci
Organizations:University of Leeds
Yorkshire Cancer Research Centenary Professor of Pathology
Honorary Consultant Histopathologist, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Cynthia Sears, MD
Organizations:Johns Hopkins University School of Medicine and Bloomberg School of Public Health
Discipline:Medicine; Infectious Diseases; Immunology
Professor of Medicine, Oncology, and Molecular Microbiology & Immunology
I am a bowel cancer survivor. In 2000, I was diagnosed with a Dukes stage 2 bowel cancer in transverse colon following an emergency presentation with a rectal haemorrhage.
I was born in the Cambridgeshire Fens in the East of England, I went to school in the Midlands, and am a Business graduate from Coventry University. I now live near Harrogate in rural North Yorkshire, UK. I had a career in industry and owned my own lighting design and distribution company for 20 years which I sold in 2015.
Since my operation I have acted as a ‘friend’ to others who are going through similar experiences with bowel cancer. A role that I get immense satisfaction from.
I am currently a Patient Advocate for Bowel Cancer Intelligence UK and Yorkshire Cancer Research and I have represented the BCI UK at the GB Colorectal Surgeons Conference, the Public Health England Conference and also the UK Government’s cross party ‘Battle against Cancer’ Conference. I also sit on the NHS Colorectal Expert Group which is charged with producing ‘The Clinical Advice for the Commissioning of the whole Bowel Cancer Pathway’.
I now willingly give my time to try and help with the improvement of the outcome of all bowel cancer patients; I feel that I am one of the lucky ones. My personal aim is to help take the luck element out of the diagnosis and treatment of this disease.
I am married with 2 adult daughters and two grandchildren. I love travelling and seeing the world, golf, cycling, art, antiques, photography, and family history research and can trace his family back to the winning side at the Battle of Hastings in 1066!
Colorectal cancer (CRC) most often occurs sporadically (as compared to genetic forms of the disease) and is one of the leading causes of cancer-related death worldwide. Environmental factors contribute substantially to CRC risk and development, particularly the intestinal microbiota. The project overall aims to understand the role of aetiologic factors in tumor development with epidemiologic features in relation to the tumor tissue microbiome. Our work package hypothesis is that Lifestyle risks, environmental exposures, diet, and cancer phenotypes are each associated with features of the colorectal cancer microbiome.
Recently, newer cancer treatments have begun to utilize the tools inherent in our immune system to better treat and control the disease. The immune system plays critical roles in the body’s response to CRC. However, it remains uncertain how this relationship between CRC and immunity differs between various bacteria. The enhancement of the activity of the immune system via changes in various lifestyle behaviors is of great interest.
Unlike genetic factors, both the microbiome and diet are modifiable and represent broadly actionable targets for CRC prevention and therapy. However, neither the causal molecular mechanisms nor corresponding microbes have been pinpointed for CRC. We thus propose to identify metabolic and genetic factors within CRC-associated microbes and their molecular regulatory consequences in the gut. We will perform the first analysis of CRC-associated microbial genetics in the largest collection of human gut microbiomes created to date, spanning over ten different study populations. We will further assess transcriptional regulatory consequences of these microbial genetic variants and their interaction with dietary and lifestyle factors that contribute to CRC.
Work Package Leaders
Curtis Huttenhower, PhD
Organizations:Harvard TH Chan School of Public Health Boston, Massachusetts
Professor of Computational Biology and Bioinformatics
Departments of Biostatistics and Immunology and Infectious Diseases
Associate Member, Broad Institute of MIT and Harvard
Co-director, Harvard Chan Microbiome in Public Health Center
Shuji Ogino, MD, PhD, MS
Organizations:Brigham and Women’s Hospital, Harvard T.H. Chan School of Public Health/ Harvard Medical School Broad Institute of MIT and Harvard
Discipline:Molecular pathological epidemiology
Professor of Pathology, Brigham & Women’s Hospital, Harvard Medical School
Professor (Epidemiology), Harvard T.H. Chan School of Public Health
Chief Program in Molecular Pathological Epidemiology, Brigham and Women's
Associate Member, Broad Institute of MIT and Harvard
Lee Jones, MBA
Lee was diagnosed with Stage IV colon cancer in March 2004, and since undergoing several rounds of chemotherapy and a liver resection in July 2006 has been cancer free. Lee has a BA in Psychology and an MBA in Finance and had a successful executive career in government, banking, consulting, and not-for-profit organizations.
To help others to survive and thrive after a cancer diagnosis, Lee became active with Fight Colorectal Cancer as a research advocate and became a member of the Georgetown Oncology Institutional Review Board (IRB). Also, he is a patient advocate member of the SWOG Survivorship Committee and the PCORI Clinical Trials Advisory Panel (CTAP), is on the Boards of the Cancer Action Coalition of Virginia (CACV), the Ruesch Center (Georgetown University) and the Cancer Policy and Advocacy Team (CPAT) of the National Coalition for Cancer Survivorship, has been a peer research proposal reviewer for ASCO, PCORI and the DOD, and is a member of ASCO, the Colorectal Cancer Roundtable and the Alliance for Regenerative Medicine (ARM). Lee has collaborated on several projects sponsored by The Friends of Cancer Research, including defining tolerability, reporting adverse events, and tightening exclusion criteria, and has been a speaker at Ruesch Center, AAADV, CPAT and NCCN conferences.
We hope to better understand the bacterial cells that make up the colorectal cancer microbiome, and how they interact with human cancer cells. For example, what types of bacteria are found with the cancer? Do they make their way inside the human cells, or do they just sit on the surface of the cells? Do they touch human immune cells that help fight the cancer? And perhaps most importantly, do the bacteria help the cancer cells grow, and if so, how, and how can we stop them?
We are exploring these questions using specialized microscopes and technologies that enable us to see the bacteria and the human cells. We have developed methods to pinpoint locations within the intestine that harbor bacteria, and which bacteria are in each location. We are also using genome sequence analysis to help us identify the bacteria. Sequence analysis can also tell us which intestinal cell types are affected, the bacteria affecting them, and the human and bacterial genes that are turned on or off as a result of the bacterial-cancer cell association. This detailed information will give us a new understanding to aid in diagnosis of colorectal cancer and development of new treatments.
Work Package Leaders
Matthew Meyerson, MD, PhD
Organizations:Dana-Farber Cancer Institute, Harvard Medical School, Broad Institute of MIT & Harvard, Boston, Massachusetts and Cambridge, Massachusetts
Professor of Genetics and Medicine, Harvard Medical School
Director, Center for Cancer Genomics, Dana-Farber Cancer Institute
Institute Member, Cancer Program, Broad Institute of MIT & Harvard
Marios Giannakis, MD, PhD
Organizations:Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard, Harvard Medical School Boston, Massachusetts
Assistant Professor in Medicine
Marielle Santos McLeod, CPN
Marielle was diagnosed with young onset Stage III colon cancer in June 2017. After completing numerous rounds of chemotherapy is now cancer free. She holds a BA Spanish and an MHA in Healthcare Administration and has worked in the healthcare field for 13 years.
At the time of her diagnosis and treatment, she was shocked as to how little information was available regarding colorectal cancer in young adults. After losing her job while undergoing chemotherapy, she made it her mission to bring awareness to this disease that almost claimed her life. She began her career as a Certified Bilingual Patient and Family Support Navigator at the Colorectal Cancer Alliance in June 2018. While at the Alliance, Marielle has helped collaborate with the Latino Outreach Program and oversees both the Buddy Program and Blue Hope Financial Assistance Program.
The Clevers lab has been using their human ‘mini-gut’ technology. These mini guts (a.k.a. intestinal organoids) are grown in a dish from healthy gut stem cells. They can be expanded indefinitely and create miniature versions of the human gut. It has turned out that it is possible to chronically expose these mini-guts to potentially carcinogenic bacteria by weekly injections of these bacteria into the interior of the mini-guts.
Several bacterial species that are frequently found in the human intestines are suspected to contribute to the occurrence of colon cancer. One of these is a special strain (“pks”) of the best-known gut bug, E coli. In a collaboration with several other members of the consortium, it was shown that pks E coli induces unique and easily recognizable changes (‘mutations’) in the DNA of the human mini-gut cells. The same mutational signature was subsequently found to be present in the DNA of a significant fraction of human colon cancers. This ‘smoking gun’ implies that pks E coli is involved in the occurrence of a subset of human colon cancers
The Garrett Lab studies intestinal microbes and how their metabolites affect the development of bowel cancer. Short-chain fatty acids are metabolites generated by intestinal microbes from dietary fiber. In a recent publication, the Garrett Lab investigated the mechanisms by which free fatty acid receptor 2 (FFAR2), a receptor for short-chain fatty acids expressed by cancer cells and immune cells within the tumor microenvironment, afford protection from the development and progression of bowel cancer.
Work Package Leaders
Wendy Garrett, MD, PhD
Organizations:Harvard TH Chan School of Public Health/Harvard Medical School Boston, Massachusetts
Discipline:Immunology; Infectious diseases
Professor of Immunology and Infectious Diseases
Hans Clevers, MD, PhD
Organizations:Hubrecht Institute, University Medical Center Utrecht, Princess Maxima Centre for Pediatric Oncology Utrecht, the Netherlands
Discipline:Cancer research; Stem cell research
Professor of Molecular Genetics, University Medical Center Utrecht
Principal Investigator at the Hubrecht Institute (KNAW) and the Princess Máxima Center for Pediatric Oncology.
Prof Fiona Powrie, FRS
Organizations:University of Oxford
Director Kennedy Institute of Rheumatology, Translational
Gastroenterology Unit, Experimental Medicine Division Professor of
Microbiology & Immunology
The colon is the most densely populated microbial ecosystem on the planet, containing several trillion microbial cells that produce 100-fold more gene products than our human cells do. Due to the presence of these microbial organisms, the colon has a finely tuned and specialized immune system that, regretfully, may also result in increased susceptibility to cancer development and resistance to immuno-oncology therapies. Moreover, increasing evidence suggests that the microbiome may influence the efficacy and toxicity of chemotherapy drugs, and may underlie the increasing rates of colorectal cancer seen in young people under the age of 50.
Because disparate factors ranging from diet to lifestyle to medications to geography can shape an individual’s microbiome, we created a multi-center, international prospective cohort study called MICROCOSM (“Microbiome of Colorectal Cancer: Longitudinal Study of Mechanism”) to investigate how the microbiome impacts the efficacy and toxicity of cancer treatment, including immunotherapy and chemotherapy. Led by three leading academic centers (Dana-Farber Cancer Institute [Boston, MA], University of California, San Francisco, and Vall d’Hebron Institute of Oncology [Barcelona, Spain]), MICROCOSM will enroll 2,500 patients with colorectal cancer from multiple sites spanning several continents. Serial tumor, blood, and stool samples will be collected pre-, on-, and post-treatment from every patient for study of the interaction between treatment and the microbiome. Moreover, patients will complete a comprehensive and validated diet and lifestyle questionnaire once a year. The findings from MICROCOSM will lead to improved ability to select patients most likely to respond to immunotherapy and chemotherapy, decrease treatment-related side effects, and understand reasons why treatments do not or stop working. MICROCOSM will also characterize the microbiome in young-onset colorectal cancer to reveal insights into the underlying biological cause of young-onset colorectal cancer and evaluate if gut bacteria may be a factor in rising colorectal cancer incidence among younger adults.
Work Package Leaders
Kimmie Ng, MD, MPH
Organizations:Dana-Farber Cancer Institute
Associate Professor of Medicine, Harvard Medical School
Director, Young-Onset Colorectal Cancer Center
Co-Director, Colon and Rectal Cancer Center
Director of Translational Research
Center for Gastrointestinal Oncology, Dana-Farber Cancer Institute
Josep Tabernero, MD, PhD
Organizations:Vall d’Hebron Institute of Oncology
Director of Vall d’Hebron Institute of Oncology
Head of the Medical Oncology Department of Vall d’Hebron University Hospital
Director of Clinical Research at Vall d’Hebron Institute of Oncology
Co-Director of Research Unit for Molecular Therapy of Cancer-“la Caixa” at Vall d’Hebron Institute of Oncology
Head of the Gastrointestinal and Endocrine Tumors Group at Vall d’Hebron Institute of Oncology
Director of Innovation, Care and Research, Catalonian Oncology Network. Barcelona, Spain.
Professor, Medicine Department, Universitat de Vic, Universitat Central de Catalunya. Vic, Barcelona, Spain.
Candace Henley, CPN
Candace is an accomplished Foundation Executive Director with significant experience in community outreach and patient education. Superior record of successful community service and engagement. Candace is a 14-year colon cancer survivor who works to help other cancer survivors make sense of the disease as well as publicly share her story of a challenging battle with a positive attitude and faith that inspires others to never give up. Her greatest fight was against the tragic turn of events that her life took after her cancer diagnosis, which overwhelmed her, robbed her of hope, tested her faith, and threatened her with defeat. Her story will make you sad, angry, cry and cheer because it's an incredible example of perseverance and strength.
Candace advocates for “Removing Barriers for Colorectal Cancer Screening Act (H.R.1070 — 113th Congress (2013-2014), 114th Congress (2015-2016), and reintroduced H.R.1017 - Removing Barriers to Colorectal Cancer Screening Act of 2017 115th Congress (2017-2018). A Lobbyist for Right Scan Right Time, more specifically “Access to Medical Imaging” asking Congress to enact policies to save lives by expanding patient access to existing imaging technology which is a vital part of the early detection, diagnosis, and treatment of disease.
After years of advocating, Candace identified a need for grassroots awareness and education of colorectal cancer in communities of color and medically underserved communities, she started the Blue Hat Foundation in 2015. The organization utilizes community partnerships with healthcare providers, physicians, and hospital systems to deliver the message of the importance of getting screened and created and organized a faith-based colon cancer awareness campaign, Blue Hat Bow Tie Sunday, now in its 8th year. Candace has shared her story with national audiences on The Steve Harvey show, and with Katie Couric. She has contributed to several articles regarding colorectal cancer and has several articles written about her cancer journey and her tireless advocacy.
Carlos Hue, PhD
He received a degree in Psychology and Pedagogy by Complutense University of Madrid and a doctorate in Education by the University of Barcelona. He worked in a public Social Service Institute as a psychologist from1976 to 1999. Since 2000, he has been working as an Advisor for long life learning education in the Ministry of Education of the regional Govern of Aragon. Simultaneously, he has been teaching Psychology and Education for teachers and professors at the University of Zaragoza, and many other Universities in Spain.
In the last 15 years, he has become a specialist in Emotional Intelligence in Spain giving many courses to teachers, public employees, company employees, doctors, nurses, and patients. He has published two books about this subject, titled: ‘Emotional thought: a method for developing self-esteem and leadership’ and ‘Teachers’ wellbeing and emotional thought’.
He was diagnosed with colon cancer in 2003. In 2006 he became Vice President of Europacolon Spain which he continues to do. In this role, he has participated in many conferences and meetings and is studying about psycho oncology as well as coordinating a book for colon cancer patients that will be published by Europacolon Spain.
Two bacteria that can live inside the human gut, Fusobacterium nucleatum (Fn) and enterotoxigenic Bacteroides fragilis (ETBF), have been found to be related to the development of colorectal cancer (CRC). Fn can invade and live within human intestinal cells, while ETBF produces a toxin called BFT, that can also enter intestinal cells. Cells with Fn invasion or BFT toxin entry are compromised by these factors such that they are at risk to become cancerous. Both bacteria are primary examples of ‘oncomicrobes’.
However, these at-risk cells contain bacterial proteins, which should mark them for attack by immune system responses. It is currently unknown why Fn or BFT harboring cells are not sufficiently recognized and/or killed by immune cells in CRC, and whether there are differences in these immune responses between people that develop CRC and those who do not. To address this knowledge gap, we aim to firstly identify bacterial proteins our immune system can respond to, and then assess which of these most frequently leads to a sufficient immune response for elimination. Additionally, we will assess differences in immune responses to these bacteria between CRC patients and healthy controls. The results of this work will ultimately provide information that can be used to induce protective immune responses to these CRC-associated bacteria by vaccination.
Additionally, predatory bacteria, including a unique species called Bdellovibrio-and-Like Organisms (BALOs), have unique lifecycles that involve them targeting and killing their prey – other bacterial species. BALOs do not prey upon all bacterial cells, but only those with a particular type of membrane termed by microbiologists as ‘Gram negative”. Fn, ETBF and another oncomicrobe, pks+ Escherichia coli, are all Gram negative, and thus potentially vulnerable to attack by BALOs; meanwhile, most harmless microbes, as well as human cells, are left alone. Could we use BALOs as a type of therapy to selectively remove oncomicrobes from a person’s gut? Testing how BALOs target and destroy oncomicrobes, such as Fn, is crucial in our understanding of this dynamic and complex process. We will isolate BALOs from the environment, and ‘train’ them to improve their predatory behavior towards oncomicrobes in the human gut. The hope is to find BALO strains that can be developed into effective therapies to reduce numbers of oncomicrobes in patients with, or at risk of developing, CRC.
Can we create microbiome therapies that will displace oncomicrobes from people’s guts and therefore reduce the chance of CRC development in people at risk of this disease? This is the third challenge for our team in this work package. Here we plan a randomized, placebo-controlled trial called METRIC (Microbial Ecosystem Therapeutics in Patients with Resectable Stage I-III Colon Cancer). This pilot trial will test an encapsulated defined microbial community (NB-5) developed by Allen-Vercoe and colleagues to be given orally, like a probiotic. METRIC is designed to address the safety and tolerability, the recommended dosage, and the effect on the gut microbiome of CRC patients who receive NB-5 in this pilot clinical trial.
Work Package Leaders
Emma Allen-Vercoe, PhD
Organizations:University of Guelph Ontario, Canada
Professor and Canada Research Chair
Department of Molecular and Cellular Biology
University of Guelph
Robert Holt, PhD
Organizations:BC Cancer Agency
Scientific Co-Director, BC Cancer, Immunotherapy Program
Distinguished Scientist, BC Cancer, Genome Sciences Centre
Professor, University of British Columbia, Department of Medical Genetics,
Professor, Simon Fraser University, Department of Molecular Biology & Biochemistry
Anita Mitchell Isler
Anita Mitchell Isler was diagnosed with IV colorectal cancer at 41 years old. After learning more about her disease and family history she was determined to try to save others from this mostly preventable disease.
Her advocacy started at her children’s school, when she started a Dress in Blue Day to build awareness about the disease and guidelines. This is now held across the country on the first Friday in March.
She is a tireless advocate for colorectal cancer patients. She is the founder of Washington Colon Cancer Stars, a 501c3 which focuses on education for prevention and patient support. She has received various national awards for her work including Prevent Cancer Laurel of Advocacy Award, Colorectal Cancer Alliance (CCA) Visionary Award, National Colorectal Cancer Round Table (NCCRT) Blue Star award and local Rotary Self above service awards
She has volunteered for CCA as a buddy for 14 years and is a FCRC research advocate.
You are likely to find her wearing the Polly Polyp costume giving tours through the colon or sitting beside a newly diagnosed colorectal cancer patient. In her spare time, she is helping to raise 3 stepchildren in Woodinville Washington and enjoys spending time with her three grown children.
Barry Stein, B.Com., B.C.L., LL.B.
Barry sits on the Board of Directors of several corporations, not-for-profit organizations and foundations including Colorectal Cancer Canada, Donald Berman Foundation, Exactis Innovation, Tikva Children’s Foundation and Anzie Accessories & Design Inc.
He is a member the Board of Directors (Observer) of Quebec Clinical Research in Oncology (Q-CROC) and a member of the Board of Directors of the Canadian Personalized Healthcare Innovation Network (CPHIN). He is also a patient advisor to Alberta’s O2 Oncology Outcomes Real World Evidence Project.
Barry is the president and a Director of the Coalition Priorité Cancer au Québec. He is a founding member of the Canadian Partnership Against Cancer’s National Colorectal Cancer Screening Network (NCCSN). He also currently chairs the IQVIA Advisory Council for the Advancement of Health in Quebec.
As the president and CEO of the Colorectal Cancer Canada (CCC) he actively represents the interests of cancer patients and speaks regularly to medical professionals, industry, government, and patient groups across Canada and Internationally about colorectal cancer, Patient Values and Preferences in Health Technology Assessment, Clinical Trials and Real World Evidence, Young Adults with Cancer, Personalized Medicine and Companion Diagnostics, Biosimilars, Colorectal Cancer Screening, Foods that Fight Cancer and other CCC programs and research projects.
Meet the Patient Advocates
Each of us has extremely interesting and amazing back stories of our journeys through diagnosis, treatment and recovery of colorectal cancer, and it is this unique experience that we bring to each of the Optimisticc work packages. Many of us are also involved in various other Bowel Cancer Foundations and research activities, including the ‘Blue Hat and Bow Tie Foundation’ founded by Candace Henley, the Washington Colon Cancer Stars founded by Anita Mitchell Isler, Colorectal Cancer Canada led by Barry Starr, Europacolon Spain led by Carlos Hue, and more! Please take a look at our bios for more information.