March 10, 2017
A drug that treats rheumatoid arthritis, leflunomide, inhibited a metabolic pathway to kill tumors in breast melanoma cells implanted in mice.1
Leflunomide is a pyrimidine synthesis inhibitor it really is an immunosuppressor. The FDA authorised its use for the medicine of rheumatoid arthritis and psoriatic arthritis.
Researchers found out that leflunomide can inhibit a metabolic pathway that occurs in tumors with mutations in PTEN. PTEN (phosphatase and tensin homolog) is a tumor suppressor gene, and mutations during this gene take place in lots of cancers.
results from this analysis might present a new remedy for aggressive cancers with few medication alternatives.
This study revealed how a mutation in PTEN impacts a metabolic pathway in cancerous cells. PTEN-mutant cells required more glutamine, which in turn sped the production of DNA and brought about unregulated tumor proliferation.
because these cells grew to be elegant on a glutamine flux via new synthesis of pyrimidine, this caused sensitivity to the inhibition of dihydroortate dehydrogenase. Leflunomide inhibits dehydroortate dehydrogenase and damages the DNA generated within the pathway.
When researchers administered leflunomide in vitro and in vivo, PTEN-mutant cells died and match cells remained alive.
The researchers transplanted human breast cancer cells into mice to look at various the efficiency of leflunomide. Administration of leflunomide resulted in massive reductions in tumor size.
These consequences suggest a possible remedy for aggressive, PTEN-mutant cancers. many of these cancers, comparable to triple-bad breast cancer and glioblastoma, have few cures.
Reference
1. Mathur D, Stratikopoulos E, Ozturk S, et al. PTEN regulates glutamine flux to pyrimidine synthesis and sensitivity to dihydroorotate dehydrogenase inhibition. cancer Discov. 2017 Mar 2. doi: 10.1158/2159-8290.CD-16-0612 [Epub ahead of print]
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