Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : firstname.lastname@example.org
|Ref Type||Journal Article|
|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|
|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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|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|