London: A well-known drug for rheumatoid arthritis can more effectively treat melanoma when combined with traditional therapy for the most deadly form of skin cancer, a study has found.
Scientists at the University of East Anglia (UEA) in the UK found that in mice, using the two treatments together almost completely stopped the growth of a melanoma tumour.
Although only five per cent of skin cancer cases involve melanoma, it causes the majority of deaths from the disease.
If caught early, melanoma is treatable, but once the cancer has metastasised or spread, then treatment becomes more difficult.
In recent years, a number of new treatments have been developed for metastatic melanoma, some targeting certain genetic mutations.
However, the disease can quickly become resistant to most drugs, so research is focusing on combinations of treatments, said Grant Wheeler from UEA.
"By combining therapies, it's possible to attack the disease from several angles, which makes it harder for the melanoma to develop resistance to any of the drugs," said Wheeler, lead researcher of the study published in the journal Oncotarget.
"Our research has shown that there could also be further benefits - by joining these two drugs together you may be able to enhance their effects, getting a treatment that is more than the sum of its parts," said Wheeler.
Researchers focused on leflunomide, an immunosuppressive drug approved for treatment of rheumatoid arthritis.
Previous research by the team had shown it to be effective in use with drugs that target melanoma with a certain genetic mutation, known as BRAFV600E.
The new study discovered more about how leflunomide works against melanoma and tested it in combination with another melanoma drug, selumetinib.
Selumetinib is one of a number of drugs that target the activity of a protein called MEK, to which melanoma is addicted for its survival.
MEK inhibitors are already used in combination with BRAF inhibitors to combat resistance, but the research shows that adding leflunomide to the mix may make it even more effective.
When the team tested leflunomide in the lab, it was found to work on melanoma cells irrespective of the genetic signature of the cancer.
This means that leflunomide has the potential to be used in all melanoma cases, not just for tumours harbouring BRAF mutations.
The team looked specifically at how leflunomide was acting on the melanoma cells and found that it was able to stop the cells in an early phase of their growth and then force them to kill themselves, a process known as apoptosis.
However, when scientists tested leflunomide on melanoma cells jointly with selumetinib, they found it was more effective than either drug on its own.
The finding was replicated in tests on mice with melanoma tumours: using the two drugs together almost completely halted the growth of the tumour over a 12 day period, which far outstripped the effect of either drug used in isolation.
However, further research is required before this combination can go into clinical trials, including testing whether melanoma can develop resistance to the treatment....