Novel Targeted Therapies for Inflammatory Breast Cancer
Technical Report,30 Sep 2018,29 Sep 2019
Mount Sinai School of Medicine New York United States
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Inflammatory breast cancer IBC, tilde5 percent of all breast cancers is the most lethal form of breast cancer, presenting a 5-year survival rate that is less than half of the non-IBC patients. Remarkably, we have found that survival of IBC cells depends on histone deacetylase 6 HDAC6 function. Here, first, we used these state-of-the-art system biology approaches to evaluate the response to ACY-1215 of a large series of breast cancer cells sensitive and resistance to identify critical hubs associated with resistance to HDAC6 inhibition. Through our studies we have found that STAT3 signaling is strongly upregulated in resistant cell lines upon inhibition HDAC6 suggesting an adaptative survival mechanism of the treated cells. Importantly STAT3 inhibitors such as Ruxolitinib already exist and can be easily translated to the clinic. Thus, our studies identified STAT3 inhibition as the prime candidate to synergistically interact with Ricolinostat. Additionally to STAT3, other pathways such as P38, TGF-Beta, and AKT has also emerged as MRs.
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