HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Vorinostat downregulates CD30 and decreases brentuximab vedotin efficacy in human lymphocytes.

Abstract
With an increasing number of clinical trials looking at combination therapies in cancer, potential drug-drug interactions require particular attention. One such instance is the treatment of CD30(+) tumors after previous vorinostat (SAHA; suberoylanilide hydroxyamic acid) failure with the anti-CD30 antibody-drug conjugate brentuximab vedotin. Using B-, T-, and natural killer (NK)-cell lines in vitro, we demonstrate that SAHA downregulates the expression of CD30 and lowers the efficacy of subsequent brentuximab vedotin treatment if baseline CD30 levels are reduced by 50% or more. Interestingly, low-dose SAHA treatment that maintained 50% or more of basal CD30 expression followed by subsequent treatment with brentuximab vedotin led to enhanced antitumor activity. The downregulation of CD30 was short lived upon SAHA removal, suggesting that allowing SAHA washout may circumvent any interactions with subsequent drug therapies. Our findings confirm the requirement of CD30 for brentuximab vedotin efficacy and suggest that combination treatment with SAHA in CD30(dim) tumors may decrease efficacy. Combination treatment in highly CD30(+) tumors, however, increases efficacy and warrants further consideration as a new treatment paradigm.
AuthorsZainul S Hasanali, Elliot M Epner, David J Feith, Thomas P Loughran Jr, Clare E Sample
JournalMolecular cancer therapeutics (Mol Cancer Ther) Vol. 13 Issue 12 Pg. 2784-92 (Dec 2014) ISSN: 1538-8514 [Electronic] United States
PMID25319394 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright©2014 American Association for Cancer Research.
Chemical References
  • Hydroxamic Acids
  • Immunoconjugates
  • Ki-1 Antigen
  • RNA, Messenger
  • RNA, Small Interfering
  • Vorinostat
  • Brentuximab Vedotin
Topics
  • Brentuximab Vedotin
  • Cell Line, Tumor
  • Cell Membrane (metabolism)
  • Drug Antagonism
  • Gene Expression Regulation (drug effects)
  • Gene Knockdown Techniques
  • Humans
  • Hydroxamic Acids (pharmacology)
  • Immunoconjugates (pharmacology)
  • Ki-1 Antigen (antagonists & inhibitors, genetics)
  • Lymphocytes (drug effects, immunology, metabolism)
  • RNA, Messenger (genetics)
  • RNA, Small Interfering (genetics)
  • Vorinostat

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: