Novel Targeted Therapies for Inflammatory Breast Cancer
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 of a large series of breast cancer cells to the HDAC6i ricolinostat 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. Additionally, our mechanistic studies have recently discovered that HDAC6 inhibition compromised cell viability through down-regulation of c-MYC. Our discoveries represent an exciting framework to transition the use of HDAC6i to the clinic.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2021
- Accession Number
- AD1119503
Entities
People
- Jose Silva
Organizations
- Icahn School of Medicine at Mount Sinai