Panobinostat Synergizes with Chemotherapeutic Agents and Improves Efficacy of Standard-of-Care Chemotherapy Combinations in Ewing Sarcoma Cells

Abstract

There has been little improvement in Ewing sarcoma survival rates over the past several decades and new therapeutic options are desperately needed. Histone deacetylases (HDACs) are known to play a role in cancer development and progression. We show that HDAC2 is overexpressed in Ewing sarcoma cells and that an HDAC inhibitor, Panobinostat, is cytotoxic to Ewing sarcoma cells both alone and when combined with standard of care. Mechanistically, we show that Panobinostat increases the DNA damage caused by standard of care leading to the death of the Ewing sarcoma cells. We believe that HDAC inhibition combined with standard-of-care chemotherapeutics may be an effective treatment option for Ewing sarcoma patients.