Diagnostic test step closer

A urine test developed by scientists at the University of Cambridge has moved a step closer to clinical use following new findings revealing it could do more than first thought.

Originally designed to detect early signs of lung cancer and treatment resistance, the latest results show potential in identifying biological signals associated with pulmonary fibrosis – a serious condition where early diagnosis remains a major challenge.

The work, supported by Cancer Research UK, builds on the group’s research into senescence biology and has seen them develop a tiny sensor system designed to report on senescence-associated activity in the body. Cellular senescence – often referred to as ‘zombie cells’ because they stop dividing but remain metabolically active – is increasingly recognised as a hallmark of both cancer and a range of age-related diseases.

The latest study, published in Nature Aging, demonstrates the system’s use as a tool for tracking this biological signal in lung cancer models, alongside evidence that the same activity is also present in experimental models of pulmonary fibrosis.

Rather than detecting cancer directly, the system measures a biochemical signal associated with senescence-related processes in diseased lung tissue. Matrix metalloproteinase-7 (MMP-7) was identified as a key marker linked to senescence-associated activity in lung cancer biology, particularly in the context of therapy response, and is also observed in pulmonary fibrosis.

The nanoprobe, called ALBANC, is made of a human serum albumin protein linked to gold nanoclusters through MMP-7-cleavable peptide linkers. When the sensor encounters elevated MMP-7 activity in diseased tissue, the gold nanocluster link is cut and these tracers are released into circulation, enabling renal excretion. These fragments are small enough to be filtered by the kidneys and appear in urine, where they form the measurable colorimetric signal.

To improve sensitivity, the team developed a nanoparticle growth-based amplification step that enhances detection of the urinary signal by approximately 250-fold compared with conventional approaches. This allows repeated, non-invasive measurement over time, and tracking of senescence-associated biology in preclinical models.

Professor Ljiljana Fruk, of the BioNano Engineering research group at the Department of Chemical Engineering and Biotechnology, Cambridge, said the strength of the approach lies in translating a complex and otherwise inaccessible biological process into a measurable signal.

She said: “This approach allows us to follow senescence-associated activity in a way that is non-invasive and repeatable. It was already very exciting to be developing a system that could report on biological signals linked to lung cancer and treatment response, with the goal of improving how disease is monitored and ultimately outcomes for patients. The fact that it may also be relevant to other conditions we did not originally set out to study makes the direction of research particularly encouraging.”

Professor Daniel Muñoz-Espín, of the Early Cancer Institute at Cambridge and co-Director of the CRUK Cambridge Centre Thoracic Cancer Programme, said the findings extend the potential of the nanosensor beyond lung cancer alone.

“In addition to its application in monitoring lung cancer biology, including therapy resistance and disease progression, our work shows that the system can also report on biological signals associated with pulmonary fibrosis. This is particularly important given the severity of the disease and the lack of effective early intervention once it becomes established. A non-invasive way to track disease-related biology over time could be valuable in patients at higher risk, including those with underlying lung conditions, environmental exposures or other known risk factors,” he said.

Professor Robert Rintoul of the Department of Oncology, Cambridge and co-lead for the CRUK Cambridge Centre Thoracic Cancer Programme said: "Novel approaches for lung cancer detection and response to treatment are urgently needed to improve patient outcomes. This work forms the basis for testing within clinical trials with a view to future use in the clinic."

Using patient samples, murine models and large genomic datasets, the researchers have demonstrated that MMP-7 is the key biomarker associated with senescence-linked biological activity. The study further showed that the nanosensor can track these signals in preclinical lung cancer models.

Importantly, the same MMP-7–associated signal was also detected in experimental models of pulmonary fibrosis at early stages, a condition characterised by progressive and often irreversible lung damage and linked to elevated MMP-7 levels in patients. This reflects the shared underlying biology of senescence-associated tissue activity across different disease contexts, rather than a cancer-specific mechanism.

Work is now progressing towards clinical trials to evaluate how reliably the nanoprobe can report MMP-7–associated biological activity in patients, and whether it could be developed into a tool for monitoring lung cancer progression, treatment response and related fibrotic disease.

This latest study forms part of the team’s wider research into lung cancer, following related work published earlier this year exploring how chemotherapy-induced ‘zombie cells’ may help cancers resist treatment and return.