Accession Number : AD1048465


Title :   Novel Targeted Therapies for Inflammatory Breast Cancer


Descriptive Note : Technical Report,30 Sep 2016,29 Sep 2017


Corporate Author : Icahn School of Medicine at Mount Sinai New York United States


Personal Author(s) : Silva, Jose


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1048465.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 9


Abstract : Inflammatory breast cancer (IBC, 5% 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-, and AKT has also emerged as MRs.


Descriptors :   inflammation , breast cancer , inhibition , cell line , neoplasms , enzymes


Subject Categories : Medicine and Medical Research
      Biochemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE