In the treatment of melanoma, tumor cells sometimes develop a resistance to anticancer drugs. A new study asks whether an antibiotic may provide extra firepower to bolster existing treatments.
Accounting for about 1 percent of skin cancers, specialists diagnose more than 90,000 new melanomas each year in the United States.
Worryingly, melanoma rates have been slowly climbing over the past 30 years.
Many cases are successfully treated but, because of the steady rise in prevalence, it is increasingly important to design the most effective treatment possible.
Picking off the troublemakers
In melanoma tumors, cells differ; some are highly susceptible to existing cancer treatments, such as BRAF and MEK inhibitors, while others quickly become resistant to these drugs, supporting the growth and spread of the tumor.
Finding ways to tackle these most troublesome cancer cells is of utmost importance.
Scientists previously showed that the most difficult-to-treat cells produce particularly high levels of an enzyme called aldehyde dehydrogenase 1 (ALDH1).
Using this as a starting point, experts sought ways to block ALDH1 production, and the new study pushes the boat out further, aiming to weed out and destroy all cells that secrete high levels of ALDH1.
The team — at the Medical Research Council Institute of Genetics and Molecular Medicine at the University of Edinburgh in the United Kingdom — focused on nifuroxazide, an antibiotic. It was initially patented in the 1960s and is typically used to treat colitis and diarrhea.
Their findings were published this week in the journal Cell Chemical Biology.
Old drugs, new tricks
The team implanted human melanoma samples into mice and then treated them with nifuroxazide. As expected, the antibiotic selectively killed tumor cells that produced higher levels of ALDH1 but did not damage other cell types.
For the next step, they treated the tumor with standard cancer drugs — BRAF and MEK inhibitors — and the number of cells producing higher levels of ALDH1 increased and became particularly sensitive to nifuroxazide.
If further studies reach similar conclusions, we could use nifuroxazide alongside BRAF and MEK inhibitors, mopping up the more dangerous cancer cells.
"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."
Lead researcher Dr. Liz Patton
She continues, "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."
Nifuroxazide is a well-used drug, but there are still many hurdles to clear before it can be used to treat cancer in clinical trials; as Dr. Patton outlines:
"It's great that this antibiotic is approved for use in humans, but it wasn't designed as a cancer drug, so we still need to find out if it's safe and effective for cancer in humans — for example, can it get to the cancer in the body and are the doses needed safe? We may need to take the concept for how this antibiotic works and re-design it to make it better at killing cancer."
Dr. Nathan Richardson, the head of molecular and cellular medicine at the Medical Research Council, is excited at the prospect.
He says, "This imaginative study exploits the sensitivity of some cancer cells to an existing antibiotic and could reveal an exciting new approach to both combination treatment and 'personalized' medicine by directly targeting drug resistance."
Drug resistance is a significant stumbling block in the treatment of many cancers; hopefully, however, this type of approach could also help researchers tackling other types of cancer.