'Old' antibiotic could treat melanoma
Friday October 5th, 2018
An old antibiotic could help to treat melanoma, British researchers have reported.
Scientists from the Medical Research Council (MRC) Institute of Genetics and Molecular Medicine
at the University of Edinburgh have found that in mice and in samples from human tumours, nifuroxazide
could selectively kill dangerous cells within melanomas.
It is known that many of the more dangerous cells in melanoma tumours produce aldehyde dehydrogenase
1 (ALDH1) and much recent research has focused on blocking the enzyme. However, in this study,
published in Cell Chemical Biology, the research team aimed to selectively kill cells producing
high ALDH1.
They used nifuroxazide, which is activated by the enzyme ALDH1, which means that it only becomes
toxic once it is inside cells producing ALDH1.
The researchers used samples of human melanomas implanted in mice and showed that nifuroxazide
killed the tumour cells that produced a lot of ALDH1, without significant toxicity to other cells
in the body.
Tumours that develop resistance to BRAF and MEK inhibitors were high in ALDH1, so the team hopes
its findings could work alongside BRAF and MEK inhibitors, which are used to treat melanomas.
In the lab, the researchers treated cancer cells lines with BRAF and MEK inhibitors, which increased
the number of cells with high levels of ALDH1 and made the cells especially sensitive to nifuroxazide
treatment.
Lead researcher Dr Liz Patton, of the MRC Institute for Genetics and Molecular Medicine, said: “There
won't be one magic bullet for targeting melanoma - the variations that exist within the cancers
mean there will need to be combination therapies.
“When people are given BRAF or MEK drugs to treat melanoma it can result in the tumours
having more cells with high levels of ALDH, so we think that's a really important target. We've
shown this antibiotic that's used mostly to target intestinal bacteria can also target and kill
cancer cells high in the enzyme ALDH1."
Sarvi et al. ALDH1 bio-activates nifuroxazide to eradicate ALDH(High) melanoma-initiating cells.
Cell Chemical Biology October 2018
https://doi.org/10.1016/j.chembiol.2018.09.005
Tags: Cancer | Dermatology | Pharmaceuticals | UK
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