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Ref Type Journal Article
PMID (22703804)
Authors Lautz TB, Naiditch JA, Clark S, Chu F, Madonna MB
Title Efficacy of class I and II vs class III histone deacetylase inhibitors in neuroblastoma.
Journal Journal of pediatric surgery
Vol 47
Issue 6
Date 2012 Jun
URL
Abstract Text Histone deacetylase (HDAC) inhibitors have shown promise in the treatment of resistant and refractory tumors including neuroblastoma. The goal of the study was to compare the efficacy of a class III HDAC inhibitor (cambinol) to a class I and II inhibitor (vorinostat).In vitro efficacy of vorinostat and cambinol, alone or in combination with doxorubicin, was assessed by 2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide calorimetric assay using both wild-type (WT) and doxorubicin-resistant (DoxR) SK-N-SH neuroblastoma cells. In vivo efficacy was determined using the same drug combinations in nude mice bearing xenograft implants of WT and DoxR cells on opposite flanks.Vorinostat and cambinol were efficacious against WT and DoxR neuroblastoma cells in vitro. In WT cells, the potency of the doxorubicin itself overshadowed any effect of cotherapy with vorinostat or cambinol. The effect of vorinostat and/or cambinol on the DoxR cells was constant across progressively increasing doses of doxorubicin. In the in vivo model, the efficacy of doxorubicin itself (88% reduction in tumor volume) again overshadowed any effect of cotreatment with vorinostat or cambinol on the WT tumors. However, in the DoxR tumors, doxorubicin alone had no efficacy, but cotreatment with either cambinol or vorinostat suppressed tumor growth (70% and 91% reduction in tumor volume, respectively).Both the class III HDAC inhibitor cambinol and the class I/II HDAC inhibitor vorinostat have efficacy against SK-N-SH neuroblastoma cells, including those resistant to doxorubicin.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Cambinol Cambinol 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown neuroblastoma not applicable Cambinol + Doxorubicin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Adriamycin (doxorubicin) and Cambinol inhibited growth of a human neuroblastoma cell line in culture and in xenograft models (PMID: 22703804). 22703804
Unknown unknown neuroblastoma not applicable Vorinostat Preclinical - Cell line xenograft Actionable In a preclinical study, Zolinza (vorinostat) displayed efficacy in human neuroblastoma cell lines in culture and in xenografts, including those resistant to Adriamycin (doxorubicin) (PMID: 22703804). 22703804
Unknown unknown neuroblastoma not applicable Doxorubicin + Vorinostat Preclinical - Cell line xenograft Actionable In a preclinical study, Zolinza (vorinostat) and Adriamycin (doxorubicin) inhibited growth of human neuroblastoma cells in culture and in cell line xenograft models (PMID: 22703804). 22703804