One of cancer researchers' top priorities is discovering ways to reduce the risk that cancer will recur or metastasize. A recent, small-scale study may have found a common, cost-effective drug that does just that.
Cancer stem cells (CSCs), also known as tumor-initiating cells, are a hot topic among researchers.
These cells are resistant to current treatments and play a significant role in both metastasis and recurrence, which are two of the biggest challenges in cancer treatment.
Because of this, finding successful ways of clearing up CSCs is of great interest.
Researchers from the University of Salford in the United Kingdom may have uncovered a treatment that could play an important role.
These scientists spend their time testing drugs that the Food and Drug Administration (FDA) have already approved. They investigate whether any existing medicines might also be able to help in the fight against cancer.
Concentrating on drugs in this way means that if they do find an existing drug that works against cancer, it could potentially reach the clinic faster.
An antibiotic repurposed
Doxycycline works by preventing cells from creating new mitochondria, which are the cells' powerhouses. Importantly, the drug has minimal side effects.
For the current study, the researchers recruited just 15 participants based at the University Hospital in Pisa, Italy. They gave nine participants doxycycline each day for 14 days leading up to surgery to remove a tumor. The remaining six participants acted as a control and took no drugs.
To assess whether the antibiotic had an impact on CSCs and the chance a tumor would recur, the scientists tested a number of biomarkers. They assessed these so-called measures of stemness in tumor tissue removed before the operation (core biopsies) and on tumor tissue excised during the procedure.
The scientists measured a significant drop in CSCs in nearly all participants who took doxycycline. Although participant numbers were very low, the results were highly significant, meaning that a clinical trial would be worth running.
Why do antibiotics work against CSCs?
Mitochondria evolved from bacteria, and antibiotics attack bacteria; this means that often, antibiotics will also target mitochondria, which prevents stem cells from reproducing.
"What we infer here is that the stem cells selectively overexpress key mitochondrial-related proteins, which means that if we can inhibit mitochondrial function, we can disrupt the stem cells."
Co-lead researcher Prof. Federica Sotgia
These findings could have significant ramifications, as co-lead researcher Prof. Michael Lisanti explains.
"We have very few FDA-approved drugs to target and reduce cancer stem cells," he says, "so to find that a drug that is effective, readily available, and costs just 10p per patient per day [...] is highly significant, particularly as around two-thirds of cancer deaths occur due to recurrence after initial treatment."
Over recent years, more and more researchers have become focused on mitochondria as a potential route to treating disease. These findings are likely to fan those flames.
This study also highlights the value of screening existing drugs for their usefulness against other conditions.
As Prof. Lisanti says, "Our ability to treat cancer can only be enhanced by utilizing drugs that are not only cheap but also widely available. Since doxycycline first became clinically available in 1967, its anticancer activity has been right under our nose, for more than 50 years."