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Old antibiotic may selectively kill lethal skin cancer cells, researchers find

Despite the lack of research being undertaken by large pharmaceutical companies into new antibiotics, scientists have discovered that by repurposing older versions, progress has been made against a type of aggressive skin cancer.

In a study published in the journal Cell Chemical Biology, scientists from the U.K.'s Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh found that an old antibiotic called nifuroxazide selectively killed dangerous cells within melanomas following tests in mice and on samples from human tumors.

Each tumor is comprised of a variety of different cells, and many of the more dangerous cells in melanoma produce an enzyme called aldehyde dehydrogenase 1, or ALDH1. To date, research into this most aggressive type of skin cancer has targeted blocking ALDH1. But the new study focused on selectively killing the cells that produce high ALDH1 using the antibiotic nifuroxazide.

The researchers showed that nifuroxazide killed the tumor cells that produced a lot of ALDH1 without significant toxicity to other cells in the body, paving the way for its use as a complementary therapy for melanoma.

Existing treatments for melanoma are called BRAF inhibitors, such as Novartis AG's dabrafenib, or Tafinlar, and Roche Holding AG's vemurafenib, or Zelboraf, and MEK inhibitors such as trametinib, also known as Mekinist, and Cobimetinib or Cotellic, among others. But some of the tumors had developed resistance to BRAF and MEK inhibitors and were found to be high in ALDH1, according to the study.

"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," said the MRC's Liz Patton, who led the research at the University of Edinburgh. "When people are given BRAF or MEK drugs to treat melanoma it can result in the tumors 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."

Still, the researchers said that although approved by regulators, the antibiotic was not designed to be used as a cancer drug, and further tests are required to ascertain its safety and effectiveness against the disease. Antibiotics are used to treat deadly infectious diseases like pneumonia and tuberculosis, as well as to enable common surgical procedures like hip replacements and heart operations and facilitate chemotherapy use in cancer patients. But an increasing resistance seen in the last 25 years has resulted in the rise of so-called "superbugs" — multidrug-resistant strains of bacteria — caused by their overuse in medicine and agriculture.

"We may need to take the concept for how this antibiotic works and re-design it to make it better at killing cancer," Patton added.

The study was funded by the MRC, the Cancer Research UK Edinburgh Centre, the European Research Council and the L'Oreal-Melanoma Research Alliance.