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Published on: January 14, 2016
Targeting of HDAC8 and investigational inhibitors in neuroblastoma
Ina Oehme1, Hedwig E Deubzer, Marco Lodrini
1German Cancer Research Center, CCU Pediatric Oncology, INF 280, D-69120 Heidelberg, Germany. i.oehme@dkfz.de
Abstract:
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.
Insights
Histone deacetylase inhibitors show promise in cancer therapy. Selective targeting of HDAC8 in neuroblastoma may improve efficacy and reduce side effects, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Histone deacetylase (HDAC) inhibitors are a novel class of anticancer drugs.
- The specific HDAC family member most relevant for cancer therapy remains largely unknown.
- Unselective HDAC inhibition in early trials has led to significant side effects.
Purpose of the Study:
- To review the clinical relevance of HDAC8 in neuroblastoma, a rare childhood cancer.
- To explore the potential of selective HDAC8 inhibition as a therapeutic strategy for neuroblastoma.
Main Methods:
- Review of existing clinical data and preclinical studies on HDAC8 in neuroblastoma.
- Analysis of the correlation between HDAC8 expression and patient outcomes.
- Comparison of the phenotypic effects of HDAC8 inhibition versus other HDAC family members.
Main Results:
- HDAC8 expression is linked to poor prognosis in neuroblastoma.
- Selective inhibition of HDAC8 promotes neuroblastoma cell differentiation.
- Targeting other HDAC family members results in distinct cellular phenotypes.
Conclusions:
- HDAC8 is a clinically relevant drug target for neuroblastoma.
- Selective HDAC8 inhibitors offer a potential strategy for neuroblastoma differentiation therapy.
- Targeting HDAC8 may reduce side effects associated with unselective HDAC inhibition.
