Sunday, June 1, 2014

Two genes may block TNBC; drugs already exist


Blocking two genes that contribute to breast cancer tumor formation may reduce the risk of triple negative breast cancer, according to a study now online at the Proceedings of the National Academy of Sciences.

The genes are MLF2 and RPL39, which work together to block nitric oxide signaling and affect blood vessel recruitment in tumors. 

Drugs already exist that can block nitric oxide signaling, which means targeted drug for some forms of TNBC may already exist.  Houston Methodist Cancer Center plans clinical trials “in the near future,” according to researchers and center director Jenny Chang, M.D. For FDA approval, drugs need to successfully perform through three stages of clinical trials, although tests on existing drugs could streamline the process.

Mutations in  MLF2 and RPL39 in human patients were associated with worse survival in triple negative breast cancer patients.

The researchers also looked at which configurations of small inhibitory RNA (siRNA) were most efficient at shutting down MLF2 and RPL39 in breast cancer stem cell lines. siRNA molecules interfere with the cell's ability to express genes and have proven to be effective drug tools for a wide variety of diseases, including some cancers.

In preliminary studies, the combination of siRNA and the chemotherapy drug docetaxel significantly reduced tumor volume relative to chemotherapy alone and also appeared to prolong survival. Separate analyses showed suppression with siRNA appeared to yield fewer metastases to lung tissue. 



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