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.
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).
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.
These results provide insights into the mechanisms of paclitaxel and glucocorticoid receptor inhibition in peripheral blood cells.
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aCommittee on Clinical Pharmacology and Pharmacogenetics
Departments of bMedicine
cHuman Genetics, The University of Chicago, Chicago, Illinois, USA
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Correspondence to Anna Di Rienzo, PhD, Department of Human Genetics, University of Chicago, 920 E. 58th Street, Rm. 424, Chicago, IL 60637, USA Tel: +1 773 834 1037; fax: +1 773 834 0505; e-mail: email@example.com or Suzanne D. Conzen, MD, Department of Medicine, University of Chicago, 5841 S. Maryland Ave., SBRI J301 MC 2115, Chicago, IL, 60637, USA Tel: +1 773 702 6149; fax: +1 773 702 0963; e-mail: firstname.lastname@example.org
Received December 21, 2013
Accepted June 8, 2014