Therapeutic Opportunities of Targeting Histone Deacetylase Isoforms to Eradicate Cancer Stem Cells

International Journal of Molecular Sciences
Peng-Chan LinChing S Chen

Abstract

Cancer stem cells (CSCs), or tumor-initiating cells, are a small subset of cancer cells with the capacity for self-renewal and differentiation, which have been shown to drive tumor initiation, progression, and metastasis in many types of cancer. Moreover, therapeutic regimens, such as cisplatin and radiation were reported to induce the enrichment of CSCs, thereby conferring chemoresistance on cancer cells. Therefore, therapeutic targeting of CSCs represents a clinical challenge that needs to be addressed to improve patient outcome. In this context, the effectiveness of pan or class-I histone deacetylase (HDAC) inhibitors in suppressing the CSC population is especially noteworthy in light of the new paradigm of combination therapy. Evidence suggests that this anti-CSC activity is associated with the ability of HDAC inhibitors to target multiple signaling pathways at different molecular levels. Beyond chromatin remodeling via histone acetylation, HDAC inhibitors can also block key signaling pathways pertinent to CSC maintenance. Especially noteworthy is the ability of different HDAC isoforms to regulate the protein stability and/or activity of a series of epithelial-mesenchymal transition (EMT)-inducing transcription factors, inc...Continue Reading

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Aug 21, 2019·Cells·Luisa BarbatoTarik Regad
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Methods Mentioned

BETA
phage display
acetylation
co-immunoprecipitation
histone acetylation

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