Neuroblastoma therapy targeting class I histone deacetylases

Coordinator:		Prof. Dr. Olaf Witt
Institution:		DKFZ Heidelberg
Homepage:		www.dkfz.de/de/PaedOnko

We identified class I histone deacetylases (HDACs) 2 and 8 as novel targets for neuroblastoma (NB) therapy. This was accomplished by whole genome expression analysis of an inducible in vitro model of neuroblastoma (NB) cell differentiation followed by the functional characterization of 100 candidate genes with medium-throughput RNA-interference (RNAi). In vivo, mRNA levels of both HDAC-2 and -8 are increased in NB tumors with unfavorable outcome compared to those with favorable outcome. In line with these findings, the cyclic tetrapeptide HC-toxin, an HDAC-inhibitor targeting class I HDACs was found to suppress the malignant phenotype of NB cells. The shift to a benign and differentiated phenotype is associated with the repression of poor-prognosis factors like high levels of N-myc and E2F-1.
Within NGFNplus, this project aims both at the further analysis of the potential of HC-toxin for NB therapy in preclinical models and the development of HDAC2- and HDAC8-selective HDACIs.


Additional relevant Internet links:
GRANT