Dr Clipson and Dr Conway have received a Cancer Research UK Biomarker Project Award to optimise and validate a Tissue-of-origin (TOO) blood test ready for biomarker qualification and clinical implementation in patients with Cancers of Unknown Primary (CUP).  

Researchers at the Centre, in collaboration with colleagues at the Christie NHS Foundation Trust, have developed a DNA methylation profiling assay that can be used with cell-free DNA (cfDNA) extracted from a simple blood test: CUPiD. In patients with cancer a small proportion of cfDNA arises from the tumour (ctDNA) – this is genetic material released from the tumour. Performing DNA methylation analysis on this material, combined with computer-based machine learning approaches, can reveal the potential origins of the cancer. This has the potential to aid diagnosis in patients with CUP, where the primary origins of their cancer remain unknown despite routine diagnostics tests. A TOO prediction from a blood test could change treatment decisions for patients with CUP without the need for an invasive biopsy. 

CUPiD was initially tested on 143 samples from patients with known cancer and made an accurate prediction 97% of the time, with a sensitivity of 85%. In a retrospective cohort of 41 patients with CUP, TOO was predicted in 32 of 41 cases. This information would have changed treatment options for the patient and could have sped up diagnosis.  

Dr Alexandra Clipson (NAB Deputy Team Lead) and Dr Alicia-Marie Conway (Academic Clinical Lecturer at the University of Manchester) are now looking to optimise the classifier and test it in 500 known tumour types to assess its performance ready for clinical implementation.   

Dr Alexandra Clipson said: ‘Translating biomarker research into the clinic and meaningful impact for patients is extremely challenging, so we are very grateful to receive the support of Cancer Research UK with this Biomarker Project Award to allow us to bridge the gap from the lab to the clinic. I am excited to continue the development of CUPiD with the talented team here at the CRUK National Biomarker Centre and Christie Hospital.’ 

Dr Alicia-Marie Conway said: ‘Patients with CUP are in desperate need of better and faster diagnosis that will enable access to treatments more specific to their individual cancer. This blood test holds real clinical promise and has an amazing team of researchers, clinicians and data scientists working on it to develop it into a meaningful test and reach the clinic. The CRUK Biomarker Project Grant is crucial to continue CUPiD development.’