A protein in tumour cells could be targeted to treat some types of aggressive cancer including brain, blood, skin, and kidney, new research has shown.
The scientists, from the Wellcome Sanger Institute, University of Cambridge and Harvard University, have identified a protein that plays a key role in transforming normal tissue into cancer, as a possible target for drug development. Inhibiting this protein effectively destroys cancer cells in laboratory models, including in cell lines and mice, while leaving healthy cells unharmed.
A scientist works with a petri dish in a lab. Image credit: NIH/NINDS
The research, published in Molecular Cell, provides strong evidence that developing drugs that block the RNA-modifying protein known as METTL1 could give people with aggressive brain, blood, skin, and kidney cancers new treatment options.
RNA-modifying proteins, in particular the METTL family, are involved heavily in cell replication. These proteins have been found in higher levels in certain cancer cells, including some brain, blood, pancreatic, and skin cancers, and are associated with poorer outcomes*.
Previously, Dr Tzelepis, along with his team at the University of Cambridge, and their collaborators at the Wellcome Sanger Institute, used CRISPR-Cas9 gene-editing technology to screen cancer cells for vulnerable points. The researchers identified the METTL1 gene – a gene that produces the RNA-modifying METTL1 protein – as a target for drug development**.
In a new study that builds on that research, researchers at the Wellcome Sanger Institute, University of Cambridge, and Harvard University have now found that mutations in the METTL1 gene which lead to higher levels of the METTL1 protein, cause the cells to replicate faster and transform into a cancerous state, producing highly aggressive tumours.
When the team inhibited the METTL1 protein by knocking out the gene, it stopped cancer cell growth while leaving the normal healthy cells unharmed, in both laboratory and mice models, suggesting it would be a good target for cancer treatments.
Recently, the team also developed a small-molecule inhibitor for a similar protein, METTL3, to help treat acute myeloid leukaemia, which will be entering clinical trials in 2022. It is hoped that this new research provides the evidence needed to start to develop a similar drug that targets METTL1, which could be used to treat a wider range of aggressive cancers if they have a mutation in the METTL1 gene or high levels of its protein.
As the METTL1 protein is elevated in cancer cells with poorer outcomes, it could also be used as a biomarker to inform treatment plans and identify those who would benefit if a drug was developed, to ensure clinical trials are as streamlined and personalised as possible.
Source: Sanger Institute