EntreMed Shares Surge as Results from Preclinical Trial for ENMD-2076 Published

EntreMed

announced today the publication of favorable results of a preclinical study in breast cancer of its oral Aurora A/angiogenic kinase inhibitor, ENMD-2076.  The article, entitled "Predictive Biomarkers of Sensitivity to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Breast Cancer Models" reports evidence that ENMD-2076 exhibited robust anticancer activity against breast cancer cell lines lacking expression of the estrogen receptor (ER), progesterone receptor (PR) and without HER2‑amplification: a particularly difficult to treat subtype termed "triple-negative" breast cancer (TNBC).  TNBC is associated with a shortened disease-free and overall survival at all stages of diagnosis when compared to other breast cancer subtypes.  Candidate predictive biomarkers were also identified which may be useful in selecting patients that are particularly sensitive to this compound, ENMD-2076, in the future.  In this study, a diverse panel of twenty-nine breast cancer cell lines representative of the clinically defined breast cancer subtypes were exposed to ENMD-2076 and the effects on proliferation, apoptosis, and cell cycle distribution were evaluated.  ENMD-2076 demonstrated more robust activity against cell lines of the TNBC subtype compared to the luminal and HER2-amplified subtypes.  This in vitro activity was confirmed in vivo, in MDA-MB-468 and MDA-MB-231 TNBC xenografts.  Baseline gene expression profiling and pathway analysis of the panel revealed that p53 and G1/S cell cycle pathways were upregulated in the more sensitive cell lines.  Within the TNBC subset itself, cell lines with a p53 mutation and increased p53 expression were more sensitive to the cytotoxic and pro-apoptotic effects of ENMD-2076 exposure than cell lines with decreased p53 expression.  This information provides the basis for a predictive biomarker strategy to explore in future clinical trials with ENMD-2076.