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(CRUK) Validation and Optimization of Prognostic Biomarker Signatures for Pseudomyxoma Peritonei


Faculty of Biology, Medicine and Health

About the Project

Pseudomyxoma peritonei (PMP) is a rare condition with an estimated incidence of 1.8 cases per 1.000.000 population characterized by peritoneal dissemination and progressive accumulation of mucinous tumour which, if untreated, is ultimately fatal.
The primary tumour in the appendix is classified as a low grade appendiceal mucinous neoplasm (LAMN) from where cells migrate and infiltrate the peritoneum resulting in the condition described as Pseudomyxoma Peritonei (PMP). Despite widespread involvement of the peritoneum no nodal or distant metastases are evident, hence aggressive locoregional treatment, including complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is offered. This procedure is widely accepted as the standard of care for PMP, as it confers an overall survival benefit of over 80% at 10 years.

Despite aggressive treatment with CRS/HIPEC, 30% of PMP patients develop recurrent disease and ultimately die with intra- abdominal disease progression. Furthermore, no systemic anticancer treatment (SACT) or targeted intraperitoneal treatment has been shown to be effective in the adjuvant setting or for advanced or recurrent disease. Little is understood about the molecular events underlying PMP and its progression. Consequently, there is an unmet need for preclinical and translational research in this condition.

We have secured a CRUK Accelerator award to establish a multicentre cohort of 408 PMP patients who have been surgically treated in five institutions highly specialized in peritoneal surface malignancies, based in UK, Italy and Spain. This collaboration allows us to generate genomic and transcriptomic data. This PhD project will involve prospective collection of blood/frozen tissue from 104 PMP patients undergoing treatment at The Christie NHSFT to be added to a further 304 samples being collected internationally through the CRUK accelerator. Whole exome sequencing (WES) will be undertaken and bioinformatics analysis performed to identify prognostic signatures to better classify PMP.

Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in relevant subject. A related master’s degree would be an advantage. 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 Non-Clinical Studentship is tenable for 4 years. We will provide running expenses, an annual stipend of £19,000 per annum and full coverage of University PhD fees at the home fee 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.


References

McMahon A, Aziz O, Willams K. Mass Spectrometry Imaging for Tumour Subtype Classification. MRC National Productivity Investment Fund (NPIF) Studentships -. Oct 2017-April 2021.

Aziz O, O’Dwyer ST. Colorectal and Peritoneal Oncology Centre Academy (establishing a program of genomic, transcriptomic, and proteomic profiles of paired patient primary colorectal cancer and peritoneal metastases). £370k Jan 2020-2025

Gurusamy K, Aziz O, O’Dwyer ST, et al. Evidence-based review of peritoneal tumour treatment using cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. NIHR HTA grant. £300k. Oct 2019-2022.

Deraco M, Aziz O, O’Dwyer S, et al. European Multicentric Project to characterise new therapeutic options for pseudomyxoma peritonei (UK, Italy, and Spain) CRUK accelerator award (£3m). Jan 2020-2025.

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