Colorectal and Peritoneal Oncology Annual Service Report 2021 - 2022

Service Report 2022 Colorectal and Peritoneal Oncology Centre – The Christie NHS Foundation Trust

comprehensive biobank of tissue from patients with pseudomyxoma peritonei (PMP) from Low grade appendiceal mucinous neoplasms (LAMNs) over 5 years.

The £2.5m award aims to identify genomic biomarkers, build in vitro 3-D models and organoids, and ultimately establish a platform to identify therapeutic options for PMP patients. Our team includes faculty from across The University of Manchester including; CPOC Lab at The Manchester Cancer Research Centre, Wellcome Trust Centre for Cell Matrix, School of Pharmacology, and Manchester Centre for Genomic Medicine. The project has to date established a standardised biobank collection process, tumour sampling, DNA and RNA extraction across the 3 countries including a quality control check. We have successfully standardised live tissue processing and cell culture leading to the development of LAMN and appendix adenocarcinoma in vitro models and organoids. Currently we are establishment of libraries of information that can be shared with researchers across the world to accelerate our understanding of LAMNs leading to PMP and optimising bioinformatics pipelines to look at this data. 5.1.2 Dysregulated pathways in ColoRectal cancer Peritoneal Metastasis (CRPM): Funding secured from The Christie Charity has allowed us to establish our CRPM biomarker research program. Our comprehensive analysis of samples from peritoneal metastases with their matched colorectal cancer primaries obtained during cytoreductive surgery has been tested and validated leading to the identification of 20 genes dysregulated in peritoneal metastases that promote an early increasing role of "stemness" in conjunction with tumour favourable inflammatory changes. Our findings have indicated that the activation of these pathways, and adaptation to the peritoneal-specific environment are key to early stages of peritoneal metastasis. We have now secured funding to increase our sample size to 200 patients, looking for prognostic signatures, and exploring these pathways to look for therapeutic options. Finally, we have also secured funding for a project on whole exome sequencing of primary colorectal cancers and their peritoneal metastases working with Professor David Wedge.

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