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New research suggests a simple blood test could improve the early detection of lung cancer

University of Leicester researchers hope earlier diagnosis could improve prognosis

New research led by scientists at the Medical Research Council (MRC) Toxicology Unit and University of Leicester suggests that, by analysing levels of tumour-derived DNA in the blood, the early detection of lung cancer could be improved.

The study, published in the journal Disease Models and Mechanisms found that, in preliminary tests using mice, a blood test could measure the circulating levels of DNA in the blood which cancer cells shed as they grow and multiply, and could even predict the presence of tumours in the lungs before they became cancerous.

Lung cancer is the number one cause of cancer-related death around the world, partly due to the difficulties in detecting the disease at an early stage. By the time lung cancer is diagnosed, it has often spread to other parts of the body making it much more difficult to treat, which is why improved diagnosis at an earlier stage is key to beating the disease.

The scientists at the University of Leicester alongside the MRC Toxicology Unit, now part of the University of Cambridge, used mice with a mutation in a gene called KRAS to model the pre-cancerous stages of lung cancer.

The researchers took regular computed tomography (CT) scans to monitor the development of small pre-cancerous lung tumours in the mice. To determine whether circulating DNA could be used to detect the tumours before they became malignant, blood samples were taken along with the CT scans at different time intervals.

The team found that the mice developing cancerous lung tumours had higher levels of circulating DNA compared with healthy mice, and that the levels of DNA released by the cancerous tumours into the blood of the mice correlated with the size of the tumours seen on the CT scans. The circulating DNA was then analysed for the presence of the precise KRAS mutation that caused the tumours to develop. The researchers found that, significantly, in later stages of tumour development where tumours were still pre-cancerous, the KRAS mutation could still be detected in circulating DNA.

Professor Catrin Pritchard, Deputy Director of Leicester Cancer Research Centre and co-author of the study said: “These findings are promising as they show that we may be able to detect premalignant lung cancer from a patient’s circulating DNA using a simple blood test.”

Professor Jacqui Shaw, Professor of Translational Cancer Genetics and Director of the Leicester Precision Medicine Institute at the University of Leicester said: “This was an investigational study in mice and more work is needed before it can be translated to humans. Future studies will need to be conducted using mice bearing pre-cancerous lesions in other tissues as well as studies using samples from humans bearing suspicious lung lesions.”

Dr Mariana Delfino-Machin, Programme Manager for Cancer at the MRC, which funded the research, added: “This is a really promising piece of early-stage research. Lung cancer is incredibly difficult to diagnose at the stage where it can be successfully treated, leading to a poor rate of survival. Developing early detection strategies to improve survival rates is key and, if this can be achieved using only a blood sample, it would greatly benefit patients and the NHS. We look forward to the results of the next stages of this research.”

The research was undertaken by two MRC-funded PhD students, Dr Callum Rakhit and Dr Ricky Trigg. The findings are presented in the paper, ‘Early detection of pre-malignant lesions in a KRAS G12D-driven mouse lung cancer model by monitoring circulating-free DNA’, published in Disease Models and Mechanisms. Dr Miguel Martins, programme leader at the MRC Toxicology Unit, Professors Pritchard and Shaw of the University of Leicester are co-corresponding authors.

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