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(MCRC Non-Clinical) The COX-2 associated inflammatory pathway as a potential biomarker for early detection in lung cancer


Project Description

Lung Cancer is the leading cause of cancer-related mortality world-wide and of pre-mature death in Manchester. Non-small cell lung cancer patients whose disease is detected sufficiently early (Stage I-IIIA) undergo surgery with curative intent, however about 40% subsequently relapse with metastatic disease. Identification of patients at greatest risk of relapse would pave the way for early therapeutic intervention. We are collecting surgical blood and tumour tissue samples from early stage lung cancer patients, with disease detected through community based screening (low dose-CTscans). A pilot screening study demonstrated that 80% of the lung cancers detected were early-stage. This samples collection will provide a unique biobank for discovery of biomarkers which inform on the risk of relapse.

Inflammation is a major factor in promotion of cancer. Zelenay and colleagues have shown that cyclooxygenase (COX)-2 driven prostaglandin-E2 production, suppresses immunity and fuels tumour promoting inflammation. In pre-clinical models, COX-2 activity dominantly reprograms the tumour immune microenvironment stimulating the production of pro-tumourigenic mediators, while suppressing IFN-signalling, natural killer cell, dendritic cell and T cell-mediated tumour elimination. Furthermore, COX-2 inhibition has synergistic anti-tumour activity when combined with immune checkpoint inhibitors. Interrogation of datasets reveals that our COX-2-associated gene inflammatory signature (COX-IS) correlates with poor prognosis across multiple cancers including lung cancer.

This project will explore the hypothesis that in early stage lung cancers COX-2 activity underlies immune evasion and pro-cancer inflammation and will investigate COX-2 signatures as biomarkers for prediction of early relapse. The aim is to identify patients who may benefit from early intervention, for example with combined COX-2 inhibitors plus immunotherapy. Inflammatory pathways and immune cells will be profiled in both screen detected and non-screen detected cancers and bioinformatics approaches used to link this with both circulating biomarker profiles and clinical data to determine associations with aggressive tumour growth and relapse.

Entry Requirements
Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage.

On the online application form select PhD Cancer Sciences. Applicants can only apply for up to TWO projects. This project has a start date of September 2020. Interviews are currently scheduled for Tuesday 25 February 2020.

Funding Notes

This Project is funded through the CRUK as part of the International Alliance for Cancer Early Detection (ACED). This four year Studentship will cover an annual stipend (currently at £19,000 per annum), running expenses and PhD tuition fees at UK/EU rates. Where international student fees are payable, please provide evidence within your application of how the shortfall will be covered (approximately £19,000 per annum).

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

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