scholarly journals Histone Deacetylase Inhibitors Delivery using Nanoparticles with Intrinsic Passive Tumor Targeting Properties for Tumor Therapy

Theranostics ◽  
2016 ◽  
Vol 6 (6) ◽  
pp. 795-807 ◽  
Author(s):  
Fatima el Bahhaj ◽  
Iza Denis ◽  
Loic Pichavant ◽  
Régis Delatouche ◽  
Floraine Collette ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Tumor Targeting ◽  
Histone Deacetylase Inhibitors ◽  
Tumor Therapy

scholarly journals Epigenetic Targeting of Autophagy via HDAC Inhibition in Tumor Cells: Role of p53

2018 ◽  
Vol 19 (12) ◽  
pp. 3952 ◽  
Author(s):  
Maria Mrakovcic ◽  
Lauren Bohner ◽  
Marcel Hanisch ◽  
Leopold F. Fröhlich
Keyword(s):  
Cell Death ◽  
Tumor Cells ◽  
Histone Deacetylase ◽  
Stress Responses ◽  
Histone Deacetylase Inhibitors ◽  
Tumor Therapy ◽  
Regulatory System ◽  
Anticancer Activities ◽  
Mutational Status

Tumor development and progression is the consequence of genetic as well as epigenetic alterations of the cell. As part of the epigenetic regulatory system, histone acetyltransferases (HATs) and deacetylases (HDACs) drive the modification of histone as well as non-histone proteins. Derailed acetylation-mediated gene expression in cancer due to a delicate imbalance in HDAC expression can be reversed by histone deacetylase inhibitors (HDACi). Histone deacetylase inhibitors have far-reaching anticancer activities that include the induction of cell cycle arrest, the inhibition of angiogenesis, immunomodulatory responses, the inhibition of stress responses, increased generation of oxidative stress, activation of apoptosis, autophagy eliciting cell death, and even the regulation of non-coding RNA expression in malignant tumor cells. However, it remains an ongoing issue how tumor cells determine to respond to HDACi treatment by preferentially undergoing apoptosis or autophagy. In this review, we summarize HDACi-mediated mechanisms of action, particularly with respect to the induction of cell death. There is a keen interest in assessing suitable molecular factors allowing a prognosis of HDACi-mediated treatment. Addressing the results of our recent study, we highlight the role of p53 as a molecular switch driving HDACi-mediated cellular responses towards one of both types of cell death. These findings underline the importance to determine the mutational status of p53 for an effective outcome in HDACi-mediated tumor therapy.

scholarly journals The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

Biomolecules ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 60 ◽  
Author(s):  
Philippe Bertrand ◽  
Christophe Blanquart ◽  
Valérie Héroguez
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Tumor Therapy ◽  
Systemic Toxicity ◽  
Oxide Shell ◽  
Cancer Drugs ◽  
Native Form ◽  
In Vivo Models ◽  
Anti Cancer

Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.

The Antiangiogenesis Role of Histone Deacetylase Inhibitors: Their Potential Application to Tumor Therapy and Tissue Repair

2020 ◽  
Vol 39 (2) ◽  
pp. 167-176 ◽  
Author(s):  
Bin Deng ◽  
Qing Luo ◽  
Alexander Halim ◽  
Qiuping Liu ◽  
Bingyu Zhang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Potential Application ◽  
Tissue Repair ◽  
Histone Deacetylase Inhibitors ◽  
Tumor Therapy

Histone Deacetylase Inhibitors in Tumor Immunotherapy

2019 ◽  
Vol 26 (17) ◽  
pp. 2990-3008 ◽  
Author(s):  
Li-Ming Zhao ◽  
Jie-Huan Zhang
Keyword(s):  
Cancer Treatment ◽  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Histone Deacetylase Inhibitors ◽  
Tumor Therapy ◽  
Relevant Literature ◽  
Tumor Immunotherapy ◽  
Antitumor Effects ◽  
Immune Modulators ◽  
Treatment Information

Background: With an increasing understanding of the antitumor immune response, considerable progress has been made in the field of tumor immunotherapy in the last decade. Inhibition of histone deacetylases represents a new strategy in tumor therapy and histone deacetylase inhibitors have been recently developed and validated as potential antitumor drugs. In addition to the direct antitumor effects, histone deacetylase inhibitors have been found to have the ability to improve tumor recognition by immune cells that may contribute to their antitumor activity. These immunomodolutory effects are desirable, and their in-depth comprehension will facilitate the design of novel regimens with improved clinical efficacy. Objective: Our goal here is to review recent developments in the application of histone deacetylase inhibitors as immune modulators in cancer treatment. Methods: Systemic compilation of the relevant literature in this field. Results amp; Conclusion: In this review, we summarize recent advances in the understanding of how histone deacetylase inhibitors alter immune process and discuss their effects on various cytokines. We also discuss the challenges to optimize the use of these inhibitors as immune modulators in cancer treatment. Information gained from this review will be valuable to this field and may be helpful for designing tumor immunotherapy trials involving histone deacetylase inhibitors.

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