Abstract
The activation of nuclear factor-kappaB (NFκB), a proinflammatory transcription factor, is a commonly observed phenomenon in breast cancer. It facilitates the development of a hormone-independent, invasive, high-grade, and late-stage tumor phenotype. Moreover, the commonly used cancer chemotherapy and radiotherapy approaches activate NFκB, leading to the development of invasive breast cancers that show resistance to chemotherapy, radiotherapy, and endocrine therapy. Inhibition of NFκB results in an increase in the sensitivity of cancer cells to the apoptotic effects of chemotherapeutic agents and radiation and restoring hormone sensitivity, which is correlated with increased disease-free survival in patients with breast cancer. In this review article, we focus on the role of the NFκB signaling pathways in the development and progression of breast cancer and the validity of NFκB as a potential target for breast cancer prevention and therapy. We also discuss the recent findings that NFκB may have tumor suppressing activity in certain cancer types. Finally, this review also covers the state-of-the-art development of NFκB inhibitors for cancer therapy and prevention, the challenges in targeting validation, and pharmacology and toxicology evaluations of these agents from the bench to the bedside.
Keywords: Breast cancer, inflammation, NFκB, transcription factor.
Current Medicinal Chemistry
Title:Targeting the NFκB Signaling Pathways for Breast Cancer Prevention and Therapy
Volume: 22 Issue: 2
Author(s): Wei Wang, Subhasree A. Nag and Ruiwen Zhang
Affiliation:
Keywords: Breast cancer, inflammation, NFκB, transcription factor.
Abstract: The activation of nuclear factor-kappaB (NFκB), a proinflammatory transcription factor, is a commonly observed phenomenon in breast cancer. It facilitates the development of a hormone-independent, invasive, high-grade, and late-stage tumor phenotype. Moreover, the commonly used cancer chemotherapy and radiotherapy approaches activate NFκB, leading to the development of invasive breast cancers that show resistance to chemotherapy, radiotherapy, and endocrine therapy. Inhibition of NFκB results in an increase in the sensitivity of cancer cells to the apoptotic effects of chemotherapeutic agents and radiation and restoring hormone sensitivity, which is correlated with increased disease-free survival in patients with breast cancer. In this review article, we focus on the role of the NFκB signaling pathways in the development and progression of breast cancer and the validity of NFκB as a potential target for breast cancer prevention and therapy. We also discuss the recent findings that NFκB may have tumor suppressing activity in certain cancer types. Finally, this review also covers the state-of-the-art development of NFκB inhibitors for cancer therapy and prevention, the challenges in targeting validation, and pharmacology and toxicology evaluations of these agents from the bench to the bedside.
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Cite this article as:
Wang Wei, Nag A. Subhasree and Zhang Ruiwen, Targeting the NFκB Signaling Pathways for Breast Cancer Prevention and Therapy, Current Medicinal Chemistry 2015; 22 (2) . https://dx.doi.org/10.2174/0929867321666141106124315
DOI https://dx.doi.org/10.2174/0929867321666141106124315 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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