Identifying Novel Therapeutic Targets and Treatments for Colorectal Cancer

Dr Elizabeth Mann is a postdoctoral researcher in Fiona Powrie’s muscosal immunology group, based at the Kennedy Institute of Rheumatology (within the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences). Beth did her Master’s and PhD in Immunology in the MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, based at King’s College London.

Beth and her fellow researchers are interested in novel approaches to treat colorectal cancer, focussing on treatment-refractory patients. In particular, they are looking to better understand the intricate roles of the immune system and microbiome in cancer so that we can target these to improve treatment. Humans are colonised by an ecological community of microorganisms that outnumber host cells and are highly enriched in the gut. Normally, these commensals have a symbiotic relationship with the host, but there is growing evidence that changes to its composition may be a causing factor for many diseases, including cancer, making the microbiome a potential therapeutic target. The hope is that Beth’s work will identify novel therapeutic targets and treatments that, importantly, will be beneficial for those patients who current treatment options offer little curative potential.

One aspect of Beth’s project funded by CRUK is part of an international collaboration, which aims to manipulate the microbiome to beat colorectal cancer, called OPTIMISTICC (OPportunity To Investigate the Microbiome’s Impact on Science and Treatment In Colorectal). As part of this consortium the role of the Oxford team is to look mechanistically at how the microbiome alters tumour biology. One way they will do this is by growing organoids, which are self-renewing 3D tissue cultures, using stem cells from patients and looking at how adding different microbes impacts their function. This system can also be used to look at interactions with the immune system as well as therapies that are currently approved for colorectal cancer treatment.
Furthermore, Beth is contributing to the establishment of a phase 0 clinical trial in which the aim is to target one aspect of the immune system, which is believed to be detrimental in a subset of colorectal cancer patients. The researchers are currently planning the trial which is aimed at assessing safety and determining biologically whether they can see any effect of the treatment in tumour tissue by looking at biopsies.

Across several projects Beth is collaborating with a vast number of researchers: within the CRUK Grand Challenge (a list of all researchers involved can be found on the OPTIMISTICC website), Beth is also closely collaborating with Prof. Tim Maughan (Department of Oncology) and the S:CORT team, several colleagues in OCTO are helping to facilitate the clinical trials.

Beth’s work is funded by CRUK (Grand Challenge) and the MRC (Experimental Medicine Challenge Grant).