OPTIMISTICC

Challenge

Improve treatment responses by manipulating the composition and status of the microbiota 

Researchers
14
Principal Investigator
Professors Matthew Meyerson and Wendy Garrett
Location
Canada, the Netherlands, Spain, USA and UK 
Funded By
Cancer Research UK - £20m
Specialisms
Genomics, microbiology, genetics, immunology, biology, epidemiology, pathology

Manipulating the microbiome

It’s becoming increasingly clear that bowel cancer – the third most common cancer worldwide – is intricately linked to microbes in the gut. By exploring how these microbes drive cancer and influence a person’s response to treatment, the OPTIMISTICC team could transform outcomes for people around the world.   

A delicate balance

Funded by:

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The human body is home to trillions of different microorganisms, including bacteria, fungi and viruses. Together, they form the microbiome – a community of microbes differing from organ to organ and person to person.   

For the most part, the relationship between the microbiome and the body is mutually beneficial, especially in the gut. In return for a protected, nutrient-rich environment, bacteria assist with digestion and provide protection from pathogenic microorganisms. To live in harmony with this vast microbial metropolis, the immune system works constantly to ensure good bacteria are tolerated, and harmful species are eliminated.   

It’s a delicate balance, perturbations to which are associated with the development of several diseases, including bowel cancer. It’s also becoming increasingly clear that the microbiome affects how people with cancer respond to their treatment. Understanding the complex relationship stacks up to a monumental global challenge.   

Enter OPTIMISTICC: an international team with a diverse range of complementary expertise. Their goal is to pinpoint how the microbiome impacts the initiation and development of bowel cancer, translating their findings into strategies that could transform outcomes for people with the disease.

Professor Matthew Meyerson, Joint Principal Investigator, OPTIMISTICC

Professor Matthew Meyerson, Joint Principal Investigator, OPTIMISTICC

Professor of Genetics and Medicine and Director of the Center for Cancer Genomics

The role of the cancer microbiota remains one of the big mysteries in cancer biology. We are excited that our proposal will be supported by Cancer Grand Challenges as it will enable our team to transform understanding of how the colon cancer microbiome influences cancer growth, diagnosis and response to treatment.

The whole research pipeline: from data to the clinic

A crucial first step is to develop a vast, integrated dataset, exploring the link between a person’s risk of cancer, their gut bacteria and their lifestyle. Size matters for studies like this and the team is analysing samples and information from 17,000 people from around the world, with or at risk of bowel cancer. This dataset will provide, for the first time, a clear picture of how the microbiome convenes with other factors to determine a person’s risk of bowel cancer, potentially identifying new ways to prevent the disease.   

In the lab, the team will map how the microbiome interacts with cancer cells to drive the development of the disease. Which cells are targeted by which species of bacteria? Do bacteria exert their effects inside the cells or on their surface? They’ll also interrogate how the microbiome interacts with the immune system to understand why immunotherapies have, so far, been ineffective for most people with bowel cancer.  

Closer to the clinic, the team will analyse blood, tumour and stool samples from bowel cancer patients all over the world, layering this information with detailed clinical and lifestyle data. The result will be a one-of-a-kind resource for the global research community to explore how the microbiome impacts – and is itself impacted by – treatment.   

Professor Wendy Garrett and colleague

The microbiome: a therapeutic treasure trove

Finally, the team will run a cohort study to explore the therapeutic potential of the microbiome and answer key questions. Could a microbial cocktail provide an effective way to treat bowel cancer? What is the safest, most effective way of administering this in patients?   

The scope of OPTIMISTICC’s plan is unprecedented. Within 5 years, they aim to have revolutionised understanding of the role the microbiome plays in cancer development, found new ways to prevent bowel cancer and defined new treatment strategies that manipulate the microbiome. And while their project is focused on bowel cancer, the team is confident their findings could open new avenues of exploration for many other types of the disease.   

Predators: a new addition to our arsenal?

OPTIMISTICC will also investigate a curious class of microbes, collectively known as predatory bacteria. While they pose no risk to human health, they seek out and target other bacteria – their preference of which can be manipulated – and could represent an intriguing way to wipe out certain cancer-causing species.   

Professor Wendy Garrett, Joint Principal Investigator, OPTIMISTICC
Professor Matthew Meyerson, Joint Principal Investigator, OPTIMISTICC
Professor Emma Allen-Vercoe
Hans Clevers
Dr Marios Giannakis
Professor Robert Holt
Dr Curtis Huttenhower
Professor Kimmie Ng
Professor Shuji Ogino
Professor Fiona Powrie
Professor Philip Quirke
Professor Cynthia Sears
Dr Josep Tabernero
Dr Laura Porter
Anita Mitchell Isler
Candace Henley
Barry Stein
Marielle Santos McLeod
Carlos Hue
Lee Jones
John Barnes