Targeting of HDAC8 and investigational inhibitors in neuroblastoma.
Histone deacetylase (HDAC) inhibitors are an emerging class of promising novel anticancer drugs. However, little is known which one of the 11 classical HDAC family members is the most relevant drug target for therapy. The first Phase I/II trials show that unselective inhibition of HDACs causes a variety of side effects. Therefore, identification and selective targeting of the most critical tumor entity-relevant HDAC family member may reduce unspecific effects and increase antitumor efficacy in the future. Here, we review the clinical relevance of a particular HDAC family member, HDAC8, in neuroblastoma biology, a highly malignant embryonal childhood cancer. HDAC8 expression correlates with poor outcome in neuroblastoma and selective HDAC8 inhibition induces differentiation. In contrast, the targeting of other HDAC family members results in a completely different phenotype. Because HDAC8-selective inhibitors are available, HDAC8 may be a potential drug target for neuroblastoma differentiation therapy using selective inhibitors, avoiding unspecific side effects.
German Cancer Research Center, CCU Pediatric Oncology, INF 280, D-69120 Heidelberg, Germany. i.oehme@dkfz.de
Ina
I
Oehme
Hedwig E
HE
Deubzer
Marco
M
Lodrini
Till
T
Milde
Olaf
O
Witt
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000503:physiopathology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
D000970:Antineoplastic Agents; D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases