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Response of Merkel cell polyomavirus-positive Merkel cell carcinoma xenografts to a survivin inhibitor

Dresang, LR and Guastafierro, A and Arora, R and Normolle, D and Chang, Y and Moore, PS (2013) Response of Merkel cell polyomavirus-positive Merkel cell carcinoma xenografts to a survivin inhibitor. PLoS ONE, 8 (11).

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Abstract

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer associated with high mortality. Merkel cell polyomavirus (MCV), discovered in 2008, is associated with ∼80% of MCC. The MCV large tumor (LT) oncoprotein upregulates the cellular oncoprotein survivin through its conserved retinoblastoma protein-binding motif. We confirm here that YM155, a survivin suppressor, is cytotoxic to MCV-positive MCC cells in vitro at nanomolar levels. Mouse survival was significantly improved for NOD-Scid-Gamma mice treated with YM155 in a dose and duration dependent manner for 3 of 4 MCV-positive MCC xenografts. One MCV-positive MCC xenograft (MS-1) failed to significantly respond to YM155, which corresponds with in vitro dose-response activity. Combination treatment of YM155 with other chemotherapeutics resulted in additive but not synergistic cell killing of MCC cell lines in vitro. These results suggest that survivin targeting is a promising therapeutic approach for most but not all MCV-positive MCCs. © 2013 Dresang et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Dresang, LR
Guastafierro, A
Arora, R
Normolle, Ddpn7@pitt.eduDPN70000-0001-8675-5014
Chang, Yyc70@pitt.eduYC70
Moore, PSpsm9@pitt.eduPSM9
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorGao, Shou-JiangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 18 November 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 11
DOI or Unique Handle: 10.1371/journal.pone.0080543
Schools and Programs: Graduate School of Public Health > Biostatistics
Refereed: Yes
Date Deposited: 30 Jan 2014 18:07
Last Modified: 06 Sep 2018 18:55
URI: http://d-scholarship.pitt.edu/id/eprint/20397

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