Removing the Unknown: Development of a rapid diagnostic blood test for Malignancies of Unknown Origin

Closing date: 09/03/2026

MB-PhD Studentship: Removing the Unknown: Development of a rapid diagnostic blood test for Malignancies of Unknown Origin

Lead Supervisors: Dr Alexandra Clipson
Co-Supervisors: Dr Alicia-Marie Conway, Dr Natalie Cook, Dr Florent Mouliere, Dr Steven Hill, Prof. Caroline Dive

Applications Deadline: Monday 9th March 2026
Interviews: Week commencing 27th April 2026
Start date: September 2026

Project Keywords: MUO, cfDNA, tissue-of-origin
Research Opportunity: MB-PhD Studentship

Project Outline

Malignancy of Unknown Origin (MUO) is the initial diagnosis when a patient presents with suspected metastatic malignant disease without an immediately identifiable primary tumour. More than half of patients diagnosed with MUO present as emergencies, which is consistently linked to poorer clinical outcomes with longer diagnostic pathways, multiple invasive investigations and acute symptom burden.

For many patients a primary tumour is identified through subsequent investigations, however this can take time and involve invasive procedures. For approximately a third of MUO cases no primary tumour diagnosis is found, and patients have a diagnosis of Cancer of Unknown Primary (CUP) (2-3% of all new cancer diagnoses).

The aim of this PhD is to design, develop and test a liquid biopsy blood test for rapid diagnosis in patients presenting with MUO. Building on existing cell-free DNA technology for predicting the tissue-of-origin for patients with CUP (CUPiD) developed at the CRUK National Biomarker Centre, this project will seek to develop and optimise the steps needed to apply it earlier in the diagnostic pathway at the first presentation of suspected MUO. Novel technologies will be tested that offer both faster clinical turnaround alongside the added potential for the detection of actionable variants to expedite access to personalised treatments.

This laboratory focussed project will be supervised by a team of clinical and scientific supervisors. Core molecular biology laboratory techniques will be acquired: cfDNA isolation, next generation sequencing, DNA methylation profiling and bioinformatic skills to support methylation and genomic sequencing analysis. In addition, there will be opportunities to learn and apply statistical analysis to a real-world clinical dataset with clinical outcome data, including evaluating survival and prognostic clinical factors within the cohort. The project is not only suited to those with academic interests in oncology, but also acute medicine, diagnostics, pathology and general practice.

Applications for this project are now open. Please complete your application on The University of Manchester Postgraduate Application Portal.

About Dr Alexandra Clipson (project Lead Supervisor)

My work focuses on the identification and development of liquid biopsy-based biomarkers in oncology. This includes the development and implementation of new technologies to maximise feature extraction from a blood draw. I have a particular interest in cfDNA methylation, harnessing the tissue- and tumour-specific patterns of methylation to elucidate the origins of cfDNA.

I stepped up to the role of Deputy Team Leader of the Nucleic Acids Biomarkers Team in 2020, having joined the CRUK National Biomarker Centre in 2017. Prior to this I was a PostDoc at the University of Cambridge working in the laboratory of Professor Ming-Qing Du investigating the genomic profiles of lymphomas, and before that my PhD was in Chemistry at the University of Edinburgh.

Alexandra Clipson headshot

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