Rheumatoid drug leflunomide shows melanoma treatment potential
December 20, 2017 Source: Sina Pharmaceutical
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];A new study from the University of East Anglia (UEA) in the United Kingdom suggests that a combination of drugs commonly used to treat rheumatoid arthritis (RA) for melanoma treatment may improve outcomes. In melanoma-bearing mice, the combination of the RA treatment drug leflunomide with the melanoma drug sumetintinib almost completely halted the growth of melanoma in mice.
Melanoma is one of the most deadly skin cancers, and although it accounts for only 5% of skin cancer cases, it causes most deaths. If found in the early stages, melanoma is completely treatable, and once the tumor metastasizes or spreads, treatment becomes more difficult.
Dr. Grant Wheeler, Principal Investigator at the UEA Biosciences Institute, said that in recent years there have been some new advances in the treatment of metastatic melanoma, some of which target specific genetic mutations. However, melanoma can rapidly develop resistance, so the current focus is on combination therapy. Through combination therapy, it is possible to attack melanoma cells from multiple angles, which will make it more difficult for melanoma to become resistant to any one drug.
Wheeler and his UEA colleagues focused on leflunomide, an immunosuppressive drug that has been approved for the treatment of RA. The team has previously demonstrated that leflunomide exhibits a higher efficacy when combined with a drug that targets a specific gene mutation, BRAF V600E. In the study, the researchers found more mechanisms of action of leflunomide against melanoma and evaluated its efficacy in combination with another melanoma drug, sumetintinib.
The team tested leflunomide in the laboratory and found it to induce apoptosis, and leflunomide worked regardless of the genetic characteristics of melanoma cells. This means that the drug is expected to be used in the treatment of all melanomas, not just melanomas that carry BRAF mutations. Leflunomide blocks the early stages of cell growth and then forces it to commit suicide, a process known as apoptosis.
Selumetinib targets the inhibition of MEK protein activity, which is important for the survival of melanoma cells. Clinically, MEK inhibitors have been used in combination with BRAF inhibitors to overcome melanoma resistance. However, it was confirmed in melanoma-bearing mice that the combination of leflunomide and selumetinib almost completely stopped the growth of the tumor in 12 days, and the effect far exceeded that of any single drug.
At the same time, the researchers warned that there are still many questions to answer before deciding whether to initiate a clinical research survey, including whether melanoma will develop new resistance to the therapy.
Dr. Wheeler said that the main problem with melanoma treatment has always been the formation of drug resistance. One way to solve this problem is through immunotherapy, which is designed to use the body's own immune defense system to fight cancer. However, there is still a clear medical need for new combination therapies in this area. We need to find new drugs that can be added to current melanoma treatment options. Leflunomide may be able to play this role.
The study was published on Oncotarget, the oncology journal on December 19, and the article reads: The anti-rheumatic drug, leflunomide, synergizes with MEK inhibition to suppress melanoma growth (Sina Pharmaceutical Compilation/newborn)
Article, picture reference source: Arthritis drug could help treat advanced skin cancer
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