Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model

Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined a CD44+/CD24−/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a critical node in self-renewal based on an ongoing lentiviral shRN...

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Main Authors:	Dave, Bhuvanesh, Landis, Melissa D., Dobrolecki, Lacey E., Wu, Meng-Fen, Zhang, Xiaomei, Westbrook, Thomas F., Hilsenbeck, Susan G., Liu, Dan, Lewis, Michael T., Tweardy, David J., Chang, Jenny C.
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412855/

id	pubmed-3412855
recordtype	oai_dc
spelling	pubmed-34128552012-08-09 Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model Dave, Bhuvanesh Landis, Melissa D. Dobrolecki, Lacey E. Wu, Meng-Fen Zhang, Xiaomei Westbrook, Thomas F. Hilsenbeck, Susan G. Liu, Dan Lewis, Michael T. Tweardy, David J. Chang, Jenny C. Research Article Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined a CD44+/CD24−/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a critical node in self-renewal based on an ongoing lentiviral shRNA screen being conducted in two breast cancer cell lines SUM159 and BT549. In corroborating work, targeting the SH2 domain of Stat3 with a novel small molecule decreased the percentage of cells expressing TIC markers (CD44+/CD24−/low and ALDH+) and mammosphere formation in p-Stat3 overexpressing human breast cancer xenografts in SCID-beige mice. Importantly, we observed a four-fold improvement in the 30-day recurrence-free survival relative to docetaxel alone with the addition of the Stat3 inhibitor in the chemoresistant tumor model. Thus, these findings provide a strong impetus for the development of selective Stat3 inhibitors in order to improve survival in patients with p-Stat3 overexpressing tumors. Public Library of Science 2012-08-06 /pmc/articles/PMC3412855/ /pubmed/22879872 http://dx.doi.org/10.1371/journal.pone.0030207 Text en © 2012 Dave et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Dave, Bhuvanesh Landis, Melissa D. Dobrolecki, Lacey E. Wu, Meng-Fen Zhang, Xiaomei Westbrook, Thomas F. Hilsenbeck, Susan G. Liu, Dan Lewis, Michael T. Tweardy, David J. Chang, Jenny C.
spellingShingle	Dave, Bhuvanesh Landis, Melissa D. Dobrolecki, Lacey E. Wu, Meng-Fen Zhang, Xiaomei Westbrook, Thomas F. Hilsenbeck, Susan G. Liu, Dan Lewis, Michael T. Tweardy, David J. Chang, Jenny C. Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model
author_facet	Dave, Bhuvanesh Landis, Melissa D. Dobrolecki, Lacey E. Wu, Meng-Fen Zhang, Xiaomei Westbrook, Thomas F. Hilsenbeck, Susan G. Liu, Dan Lewis, Michael T. Tweardy, David J. Chang, Jenny C.
author_sort	Dave, Bhuvanesh
title	Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model
title_short	Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model
title_full	Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model
title_fullStr	Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model
title_full_unstemmed	Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model
title_sort	selective small molecule stat3 inhibitor reduces breast cancer tumor-initiating cells and improves recurrence free survival in a human-xenograft model
description	Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined a CD44+/CD24−/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a critical node in self-renewal based on an ongoing lentiviral shRNA screen being conducted in two breast cancer cell lines SUM159 and BT549. In corroborating work, targeting the SH2 domain of Stat3 with a novel small molecule decreased the percentage of cells expressing TIC markers (CD44+/CD24−/low and ALDH+) and mammosphere formation in p-Stat3 overexpressing human breast cancer xenografts in SCID-beige mice. Importantly, we observed a four-fold improvement in the 30-day recurrence-free survival relative to docetaxel alone with the addition of the Stat3 inhibitor in the chemoresistant tumor model. Thus, these findings provide a strong impetus for the development of selective Stat3 inhibitors in order to improve survival in patients with p-Stat3 overexpressing tumors.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412855/
_version_	1611547909352849408

Selective Small Molecule Stat3 Inhibitor Reduces Breast Cancer Tumor-Initiating Cells and Improves Recurrence Free Survival in a Human-Xenograft Model

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