Mesothelioma is a type of cancer mainly affecting the lining of the lungs that is linked to asbestos exposure. In some countries, people that have been exposed to asbestos may be offered surveillance, but nothing is actively done to lower their risk of mesothelioma. If a safe and effective therapy was available that could prevent or delay mesothelioma development in exposed high-risk people, this could avoid a huge amount of human suffering and significantly reduce the number of deaths due to mesothelioma.
Safety and tolerability are vital considerations when selecting therapies for cancer prevention. Old generic drugs used for the management of other conditions/diseases that possess good safety profiles make excellent candidates for repurposing as cancer prevention therapies. A major benefit is that existing data can be utilized to rapidly accelerate these drugs into clinical trials, with considerable time and financial savings.
We previously tested 100 generic drugs for ability to inhibit the growth and/or kill mesothelioma cells. We identified a number of promising candidates, including the anti-worming drugs, niclosamide and mebendazole. We also found that niclosamide prevents the growth of human mesothelioma tumours transplanted into preclinical in vivo models. These two drugs warrant testing in a clinical trial to see if they have activity in humans, as a first step towards larger prevention trials. However, before we can progress to trials we need to understand how the drugs are killing mesothelioma cells and identify biomarkers (proteins that are modulated by intervention with the drugs) that can be measured in patient tissues to provide evidence of anticancer activity in humans. The aim of this project is therefore to elucidate mechanisms underlying the protective effects of these drugs, discover new biomarkers and develop methods for their analysis in human tissues. It will utilise state-of-the-art techniques including mass spectrometry-based proteomics, primary explant cultures, and immunofluorescence.
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