Gene expression of peripheral blood cells reveals pathways downstream of glucocorticoid receptor antagonism and nab-paclitaxel treatment

Joseph C. Maranville, Rita Nanda, Gini F. Fleming, Maxwell N. Skor, Anna Di Rienzo, Suzanne D. Conzen

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

OBJECTIVES: Whereas paclitaxel treatment is associated with leukopenia, the mechanisms that underlie this effect are not well-characterized. In addition, despite the importance of glucocorticoid signaling in cancer treatment, the genomic effects of glucocorticoid receptor antagonism by mifepristone treatment in primary human cells have never been described. METHODS: As part of a randomized phase 1 clinical trial, we used microarrays to profile gene expression in peripheral blood cells sampled from each of four patients at baseline, after placebo/nanoparticle albumin-bound paclitaxel (nab-paclitaxel) treatment (cycle 1), and after mifepristone/nab-paclitaxel treatment (cycle 2). RESULTS: We found that 63 genes were differentially expressed following treatment with nab-paclitaxel, including multiple genes in the tubulin pathway. We also found 606 genes that were differentially expressed in response to mifepristone; genes downregulated by mifepristone overlapped significantly with those previously identified as being upregulated by dexamethasone. CONCLUSION: These results provide insights into the mechanisms of paclitaxel and glucocorticoid receptor inhibition in peripheral blood cells.

Original languageEnglish (US)
Pages (from-to)451-458
Number of pages8
JournalPharmacogenetics and Genomics
Volume24
Issue number9
DOIs
StatePublished - Sep 2014

Keywords

  • chemotherapy
  • mifepristone
  • pharmacology
  • transcriptome

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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