Cancer drug could treat inflammatory diseases

A drug in the final testing stages to treat cancer has the potential to treat a wide range of inflammatory diseases, a new UK study has found.

Scientists at the University of Cambridge, writing in the latest edition of the Journal of Clinical Investigation, say they have identified a molecule that plays a key role in triggering inflammation in response to “potentially harmful” materials in the body.

Several of these conditions are characterised by overactivation of a component of inflammasome NLRP3 and the researchers at the Victor Phillip Dahdaleh Heart and Lung Research Institute at Cambridge report finding the PLK1 molecule that helps NLRP3 respond.

PLK1 is involved in several processes within the body, including helping to organise microtubules cytoskeletons.

Senior study author Dr Xuan Li, from the Department of Medicine at the University of Cambridge, said: “If we can get in the way of the microtubules as they try to organise themselves, then we can in effect slow down the inflammatory response, preventing it from causing collateral damage to the body. We believe this could be important in preventing a number of common diseases that can cause pain and disability and, in some cases, can lead to life-threatening complications.”

PLK1 also plays another important role in the body and scientists now believe this could hold the key to developing new treatments for inflammatory diseases.

It is already known that PLK1 is involved in mitosis, which can lead to runaway cell division and the development of tumours. Pharmaceutical companies are testing drugs that inhibit its activity as potential treatments for cancer and at least one is in phase three clinical trials, the researchers say.

When the Cambridge scientists treated mice that had developed inflammatory diseases with a PLK1 inhibitor, they found it prevented the runaway inflammatory response and at a much lower dose than would be required for cancer treatment.

They are now planning to test its use against inflammatory diseases in clinical trials.

Dr Li said: “These drugs have already been through safety trials for cancer – and at higher doses than we think we would need – so we’re optimistic that we can minimise delays in meeting clinical and regulatory milestones.

“If we find that the drug is effective for these conditions, we could potentially see new treatments for gout and inflammatory heart diseases – as well as a number of other inflammatory conditions – in the not-too-distant future.”

Professor James Leiper, associate medical director at the British Heart Foundation, which funded the trial, added: “This innovative research has uncovered a potential new treatment approach for inflammatory heart diseases such as heart failure and cardiomyopathy. It’s promising that drugs targeting PLK1 – that work by dampening down the inflammatory response – have already been proven safe and effective in cancer trials, potentially helping accelerate the drug discovery process.”

Baldrighi M, Doreth C, Li Y et al. PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models. JCI. 1 November 2023; doi: 10.1172/JCI162129


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