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Deregulated Pathways in Metachronous Colorectal Cancer Peritoneal Metastases


Faculty of Biology, Medicine and Health

, , Wednesday, September 30, 2020 Competition Funded PhD Project (European/UK Students Only)

About the Project

Over 40,000 patients are diagnosed with colorectal cancer every year in the UK. Unfortunately 40% die within 5 years with metastatic disease to the liver, lungs, and peritoneum (lining of the abdomen). Colo-Rectal Peritoneal Metastases (CRPM) affect upto 20% of patients and have a significantly reduced median overall survival (16.3 months) compared to liver (19.1 months) metastases and lung metastases (24.6 months). Oncogene mutations have been shown to predict survival in mCRC and as a result, combinations of genomic (DNA) biomarkers are used to personalise chemotherapy. In the case of CRPM, very little is known about the biomarker profile of matched primary and metastatic tumours due to lack of paired samples. One reason for this is that although CRPM may be identified at the time of diagnosis of the primary cancer (synchronous presentation) the metastases may be noted but not biopsied or removed. In addition peritoneal metastases can also occur many months or years after removal of the primary tumour (metachronous presentation). Our group have recently compared primary colorectal cancers with their synchronous CRPM, identifying a high degree of biomarker concordance. It is unclear whether this relationship also exists for metachronous CRPM.

The supervisors for this project are a team of academic clinicians (surgeons and oncologist) from the Colorectal and Peritoneal Oncology Centre (CPOC) research group based at Academy of Surgical Oncology, The Christie Hospital and the Manchester Cancer Research Centre, UK. CPOC is a high volume national peritoneal tumour service which treats over 50 CRPM patients/year using specialised cytroreductive surgery (CRS) techniques and hyperthermic intraperitoneal chemotherapy(HIPEC). This has allowed the generation of one of the world’s largest CRPM tissue biobanks fully licensed by the Human Tissue Authority. This project will access the biobank allowing the successful PhD candidate to undertake detailed molecular biological characterisation (genomic and transcriptomic) of up to 200 formalin-fixed paraffin-embedded (FFPE) paired CRPM samples (primary colorectal cancer and metastasis). Supported by a dedicated research associate they will be enabled to develop laboratory/bench skills exploring de-regulated pathways involved in the peritoneal signature of metachronous CRPM. Academic and clinical supervisors will support the integration of these laboratory pathways with the clinical database allowing translational application of the knowledge gained from these studies.

All applicants must:

• Hold an undergraduate degree in medicine
• Ideally be undergoing training in an appropriate clinical speciality

If you are interested, please make direct contact with the Lead Supervisor to discuss the project.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. You MUST also submit an online application form - choose PhD Cancer Sciences

Funding Notes

This Clinical Research Training Fellowship is tenable for 3 years. We will provide running expenses, an appropriate salary in line with the applicant’s current salary and grade, and full coverage of University PhD fees at the home rate. Where international student fees are payable, please provide evidence with your application of how the shortfall will be covered (approximately £19,500 per annum).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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