Figure 6

Model of synergism of HDACi and fenretinide in rhabdoid tumors. A. Loss of INI1 in rhabdoid tumors lead to tumor formation by deregulating different tumor pathways like cyclin D-Rb-pathway and “EZH2-stem cell program”. B. HDAC inhibition in rhabdoid tumor cell lines induces apoptotic cell death. On the other hand HDAC inhibition induces genes and pathways which are known to be already deregulated in this tumor entity (like cyclinD1 and “stem cell program”). 6. HDAC inhibition induces Rb-program by induction of CDK4/6/cyclin D1. Blocking HDAC mediated cyclin D induction by fenretinide results in dramatic induction of apoptosis. The combined inhibition of HDACs and cyclin D synergizes in the induction of apoptosis.