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Survival Benefit With Syndax Pharmaceuticals' Entinostat Maintained in Women with Advanced Breast Cancer
Date:12/7/2011

er the most common oncogenic driver is estrogen receptor signaling.  Blocking estrogen activity with aromatase inhibitors represents an effective treatment for most ER+ MBC patients, however acquired drug resistance to aromatase inhibitors leads to disease progression, ultimately requiring less effective, more toxic chemotherapies.(1)  Delaying resistance and disease progression represents a significant unmet need that could prolong survival while decreasing health care costs associated with chemotherapy and hospitalization.

About Entinostat
Syndax's lead product entinostat is a novel, oral small molecule inhibitor of class I histone deacetylases, key enzymes that alter the structure of chromatin to control gene expression. Entinostat is differentiated from other members of the class through its unique selectivity profile, pharmacokinetic properties and safety profile. Entinostat has been studied in more than 600 cancer patients where objective tumor responses have been observed in both solid and hematologic malignancies.  Breast cancer animal models demonstrated that resistance to aromatase inhibitors occurs through up-regulation of growth factor signaling pathways and down-regulation of estrogen receptor-alpha (ERα). Entinostat effectively down-regulates growth factor signaling in breast cancer cells where these pathways are active. Entinostat also up-regulates the expression of ER in breast cancer cells which have negligible or undetectable levels of ER. The ability to target multiple mechanisms of resistance establishes entinostat as a promising candidate for preventing and overcoming aromatase inhibitor resistance through epigenetic modulation. In pre-clinical testing entinostat induced tumor regression when combined with an aromatase inhibitor after the development of hormone resistance.

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SOURCE Syndax Pharmaceuticals, Inc.
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