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 language | English (US) |
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Pages (from-to) | 451-458 |
Number of pages | 8 |
Journal | Pharmacogenetics and Genomics |
Volume | 24 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2014 |
Externally published | Yes |
Keywords
- chemotherapy
- mifepristone
- pharmacology
- transcriptome
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Genetics(clinical)