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Lung squamous cell carcinoma: key molecular player discovered

Written by Jonathan Essel

Scientists funded by Cancer Research at the University of Cambridge (Cambridge, UK) have found that lung squamous cell carcinoma (LUSC) cells contain a high amount of a protein termed BCL11A. Their research demonstrated that by the manipulating the gene responsible for the protein they were able to stop the development of LUSC in a mouse model of the disease.

In the study it was revealed that BCL11A was involved in a signalling pathway, and unearthed  a potential druggable target, termed SETD8. The investigators targeted this molecule, genetically and with early forms of drugs and were able to target specific LUSC cancer cells growing in the lab and those transplanted into mice.

Due to their early discoveries further funding has been given by Cancer Research UK in order to help the development of this potential drug to target the protein, which one day could be an alternative treatment for sufferers of lung cancer.

“How LUSC develops is a bit of puzzle – until now our molecular understanding of this process was limited. Our research has revealed a major piece of this puzzle, which we are now actively trying to make new drugs against.” study author Kyren Lazarus (University of Cambridge) commented.

Whilst overall cancer survival has more the doubled over the last 40 years, the same can’t be said for lung cancer survival, which has remained rather low. A reason for this is the lack of targeted treatments for the disease, current statistics shows that just 5 in 100 individuals survive their disease for 10 or more years.

Walid Khaled ((University of Cambridge) lead author, commented: “Developing targeted treatments is a real opportunity for improving the outlook for patients.”

“With this new drug discovery grant from Cancer Research UK we are working to develop small molecules to specifically block BCL11A in LUSC cells. We are aiming to disrupt critical interactions that BCL11A has with other proteins and are working closely with our colleagues at the Department of Biochemistry in Cambridge and CRUK Beatson Institute Drug Discovery Unit to achieve this.”

Karen Vousden, Cancer Research UK’s chief scientist, concluded: “Identifying potentially druggable targets is an early yet crucial stage in the journey towards precision medicine.

“While there is much to be done before this work could be translated into patient benefit, it’s a fundamental step towards that goal and we look forward to seeing how this discovery progresses along the research pipeline.”

Sources: Lazarus KA, Hadi F, Zambon E et al. BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma doi.org/10.1038/s41467-018-05790-5 Nat. Commun.(2018)(Epub ahead of print); www.cancerresearchuk.org/about-us/cancer-news/press-release/2018-08-21-scientists-discover-first-step-towards-finding-a-new-targeted-lung-cancer-treatment