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International Research Effort May Yield New Insights into Microbiome’s Role in Colorectal Cancer
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A $25 million grant from Cancer Research UK will fund a project that aims to discover how certain microbes lead to colorectal cancer and influence response to treatment, according to a press release.
The Opportunity to Investigate the Microbiome’s Impact on Science and Treatment in Colorectal Cancer (OPTIMISTICC) project includes a research team of 14 investigators across six countries.
Matthew Meyerson, MD, PhD, director of Center for Cancer Genome Discovery at Dana-Farber Cancer Institute, and Wendy S. Garrett, MD, PhD, professor of immunology and infectious diseases at Harvard T.H. Chan School of Public Health, are co-principal investigators.
Other team members include Marios Giannakis, MD, PhD, oncologist at Dana-Farber Cancer Institute; Kimmie Ng, MD, MPH, associate professor in the department of medicine at Harvard Medical School; and Shuji Ogino, MD, PhD, MS, professor of pathology at Harvard Medical School.
International collaborators include Emma Allen-Vercoe, PhD, professor in the department of molecular and cellular biology at University of Guelph in Canada; Hans Clevers, MD, professor in the department of molecular genetics at Hubrecht Institute in the Netherlands; and Robert Holt, PhD, co-director of the BC Cancer Immunotherapy Program and distinguished scientist of BC Cancer Genome Sciences Centre at University of British Columbia.
HemOnc Today spoke with Giannakis about how this project came about, the rationale for why the microbiome may be closely linked with colorectal cancer, the timeline for results and potential implications of this effort.
Question: How did this project come about?
Answer: Several factors aligned well. The impetus of our team of international investigators is to study the role of the microbiome in colorectal cancer, with the ultimate goal of providing better therapies for patients with this disease. This remains an area of pressing clinical need. Data generated by us and others have been accumulating on the link between colorectal cancer and the microbiome and, at the same time, next-generation technologies for the study of the microbiome are now available. We can now map the microbiome in previously unprecedented detail and develop models that allow us to faithfully study the interaction between microbial and cancer cells. Thus, the timing was right for our team of international collaborators to answer the call for Cancer Research UK’s Grand Challenge.
Q: Can you describe the rationale for why the microbiome may be closely linked with colorectal cancer?
A: The colon is the most densely populated microbial environment in the world. Beyond this, the microbiome is implicated in colorectal cancer pathogenesis as well as response to cancer treatment. Specifically, there are populations of unique microbes that are present in premalignant and cancerous lesions of the colon, but not in the normal colon. This was one of the first hints that the microbiome possibly contributes to the pathogenesis of this disease. More recently, work from Dr. Meyerson’s group has identified microbial species that appear to track along from the primary cancer site to metastatic sites. Thus, through all stages of colorectal cancer development, the microbiome seems to be playing a role. Additionally, there has been an accumulating amount of evidence in the field of oncology suggesting that the microbiome can also modulate antitumor efficacy of chemotherapies and immunotherapies. This has not yet been shown in colorectal cancer, but it is one of the goals of this research effort.
Q: How will this research effort unfold?
A: Our ultimate goal is to use discoveries around the microbiome to develop novel diagnostics and therapeutics for colorectal cancer. The first objective of this grant is to define the atlas of the microbiome across time and space. We will assess how genetic and lifestyle risks impact the colorectal cancer microbiome and how this varies around the globe. For this, we will use prospective cohorts of patients with colorectal cancer and study the epidemiology of the microbiome within these cohorts. We also will examine the relationship between microbial and cancer cells in colorectal tumors.
The second objective is to figure out how the microbiome impacts cancer treatment and, conversely, how treating the microbiome changes the course of cancer. For this goal, we will use both preclinical models and prospective studies of patients with colorectal cancer. Ultimately, we hope to develop microbiome-targeted cancer therapies. An important aim of this project is also the dissemination of results within the scientific and public communities.
Q: What is the anticipated timeline for results?
A: This project is funded for 5 years, but we expect our research on the colorectal cancer microbiome to continue beyond that timeframe. We are optimistic, however, that we will make discoveries that will inform additional science, as well as come up with novel microbiome-targeted therapies for patients within the first few years of this project.
Q: What are the potential implications of this effort?
A: We expect to gain a lot more insight into the mechanisms of how the colorectal cancer microbiome impacts progression of cancer and interacts with cancer, immune cells and other components of the tumor microenvironment. We hope that this effort and discoveries that stem from it will bring attention to this understudied area of scientific investigation. We also hope to identify microbiome-based biomarkers of efficacy and toxicity to chemotherapies and immunotherapies used in colorectal cancer, as well as potential contributions of the microbiome to early-onset tumors. We will apply our findings from mechanistic studies in preclinical models and prospective cohort studies and hope to positively impact the care of patients with colorectal cancer. – by Jennifer Southall
For more information:
Marios Giannakis, MD, PhD, can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215.
Disclosure: Giannakis reports honorarium from AstraZeneca and research funding from Bristol-Myers Squibb.