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

被引：55

作者：

Dave, Bhuvanesh ^{[1
]}

Landis, Melissa D. ^{[1
]}

Dobrolecki, Lacey E. ^{[1
]}

Wu, Meng-Fen ^{[6
,7
]}

Zhang, Xiaomei ^{[6
,7
]}

Westbrook, Thomas F. ^{[4
,5
]}

Hilsenbeck, Susan G. ^{[6
,7
]}

Liu, Dan ^{[4
,5
]}

Lewis, Michael T. ^{[6
,7
]}

Tweardy, David J. ^{[2
,3
]}

Chang, Jenny C. ^{[1
]}

机构：

[1] Methodist Canc Ctr, Houston, TX USA

[2] Baylor Coll Med, Dept Infect Dis, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Radiol, Dept Infect Dis, Houston, TX 77030 USA

[4] Baylor Coll Med, Dept Radiol, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[5] Baylor Coll Med, Dept Mol & Cellular Biol, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[6] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[7] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Dept Radiol, Houston, TX 77030 USA

来源：

PLOS ONE | 2012年 / 7卷 / 08期

关键词：

STEM-CELLS; ACTIVATOR; DYNAMICS; THERAPY; TARGETS; GROWTH; ALPHA;

D O I：

10.1371/journal.pone.0030207

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：8

共 22 条

[1]

Prospective identification of tumorigenic breast cancer cells [J].