The University of Maryland study looked at the ability of entinostat to restore responsiveness of letrozole resistant MCF-7Ca xenografts to aromatase inhibitors. Entinostat was able to increase estrogen receptor expression and aromatase activity in the letrozole resistant tumors. The results suggest that entinostat may modulate Her-2 signaling and reverse the acquired resistance to letrozole caused by up-regulation of estrogen independent growth factor signaling pathways.
"While aromatase inhibitors have significantly improved the outcomes of hormone responsive post-menopausal breast cancer, not all tumors respond and many eventually acquire resistance," said Gauri J. Sabnis, Ph.D., assistant professor of pharmacology and experimental therapeutics at the University of Maryland School of Medicine. "These animal models have been confirmed in the clinic giving us hope that entinostat, if approved, will provide these women with a new treatment option to help overcome the resistance that many of them experience while on aromatase inhibitors."
Triple negative breast cancer (TNBC) is a sub-group of breast cancer that is normally unresponsive to hormone therapy as well as many forms of chemotherapy. Researchers from Johns Hopkins University School of Medicine reasoned that combining epigenetic therapy, entinostat, with differentiation therapy, retinoic acid receptor beta 2 agonist (ATRA) will provide an effective combination of drugs against TNBC. Low-doses of chemotherapy also were added to the combination. The results showed that entinostat plus ATRA and doxorubicin has the potential to be an effective treatment against TNBC.
"These findings provide encouraging new information for a non-toxic and novel combination of drugs with entinostat that could be effective in the treatment of triple negative breast cancer -- a condition desperately in need of new treatments," said Sara Sukumar, Ph.D., p
|SOURCE Syndax Pharmaceuticals, Inc.|
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