Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer

Tae-Hwe Heo; Joseph Wahler; Nanjoo Suh

doi:10.18632/oncotarget.7102

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Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer

Tae-Hwe Heo _, Joseph Wahler and Nanjoo Suh

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Oncotarget. 2016; 7:15460-15473. https://doi.org/10.18632/oncotarget.7102

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Abstract

Tae-Hwe Heo1,2, Joseph Wahler2 and Nanjoo Suh2,3

1 NP512, Laboratory of Pharmacoimmunology, Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Seoul, Republic of Korea

2 Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

3 Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

Correspondence to:

Tae-Hwe Heo, email:

Nanjoo Suh, email:

Keywords: breast cancer, interleukin-6, gp130

Received: October 05, 2015 Accepted: January 23, 2016 Published: January 31, 2016

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine with known multiple functions in immune regulation, inflammation, and oncogenesis. Binding of IL-6 to the IL-6 receptor (IL-6R) induces homodimerization and recruitment of glycoprotein 130 (gp130), which leads to activation of downstream signaling. Emerging evidence suggests that high levels of IL-6 are correlated with poor prognosis in breast cancer patients. IL-6 appears to play a critical role in the growth and metastasis of breast cancer cells, renewal of breast cancer stem cells (BCSCs), and drug resistance of BCSCs, making anti–IL-6/IL-6R/gp130 therapies promising options for the treatment and prevention of breast cancers. However, preclinical and clinical studies of the applications of anti–IL-6/IL-6R/gp130 therapy in breast cancers are limited. In this review, we summarize the structures, preclinical and clinical studies, mechanisms of action of chemical and biological blockers that directly bind to IL-6, IL-6R, or gp130, and the potential clinical applications of these pharmacological agents as breast cancer therapies.

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Reviews:

Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer

Abstract