Targeted Cancer Therapy: Giving Histone Deacetylase Inhibitors All They Need To Succeed

Gryder, Berkley E.; Sodji, Quaovi H.; Oyelere, Adegboyega K.

doi:10.4155/fmc.12.3

Cited by 334 publications

(288 citation statements)

References 139 publications

(171 reference statements)

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“…For this reason, investigation of the clinical application of HDAC inhibitors has increased with over 490 clinical trials for cancer and a few for other diseases 27 . Namely, HDAC inhibitors have also be found to be effective for treatment of other diseases.…”

Section: Histone Deacetylase Inhibitorsmentioning

confidence: 99%

Histone deacetylase inhibitors in cancer therapy. A review

Hraběta¹,

Stiborová²,

Adam³

et al. 2014

BIOMED PAP

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a Background. Despite recent success toward discovery of more effective anticancer drugs, chemoresistance remains a major cause of treatment failure. There is emerging evidence that epigenetics plays a key role in the development of the resistance. Epigenetic regulators such as histone acetyltransferases (HATs) and histone deacetylases (HDACs) play an important role in gene expression. The latter are found to be commonly linked with many types of cancers and influence cancer development. Overall, histone acetylation is being investigated as a therapeutic target because of its importance in regulating gene expression. This review summarizes mechanisms of the anticancer effects of histone deacetylase (HDAC) inhibitors and the results of clinical studies. Results. Different HDAC inhibitors induce cancer cell death by different mechanisms that include changes in gene expression and alteration of both histone and non-histone proteins. Enhanced histone acetylation in tumors results in modification of expression of genes involved in cell signaling. Inhibition of HDACs causes changed expression in 2-10 % of genes involved in important biological processes. The results of experiments and clinical studies demonstrate that combination of HDAC inhibitors with some anticancer drugs have synergistic or additive effects. Conclusions. Even though many biological effects of HDAC inhibitors have been found, most of the mechanisms of their action remain unclear. In addition, their use in combination with other drugs and the combination regime need to be investigated. The discovery of predictive factors is also necessary. Finally, a key question is whether the pan-HDAC inhibitors or the selective inhibitors will be more efficient for different types of cancers.

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Section: Histone Deacetylase Inhibitorsmentioning

confidence: 99%

Histone deacetylase inhibitors in cancer therapy. A review

Hraběta¹,

Stiborová²,

Adam³

et al. 2014

BIOMED PAP

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“…Histone deacetylase inhibitors (HDACis) have now emerged as a powerful new class of small-molecule therapeutics acting through the regulation of the acetylation states of histone proteins (a form of epigenetic modulation) and other non-histone protein targets (Gryder et al, 2012).…”

Section: Epigenetic Targetsmentioning

confidence: 99%

Endpoint of Cancer Treatment: Targeted Therapies

Topçul

Çeti̇n²

2014

Asian Pacific Journal of Cancer Prevention

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Nowadays there are several limitations in cancer treatment. One of these is the use of conventional medicines which not only target cancer cells and thus also cause high toxicity precluding effective treatment. Recent elucidation of mechanisms that cause cancer has led to discovery of novel key molecules and pathways which have have become successful targets for the treatments that eliminate only cancer cells. These so-called targeted therapies offer new hope for millions of cancer patients, as briefly reveiwed here focusing on different types of agents, like PARP, CDK, tyrosine kinase, farnysyl transferase and proteasome inhibitors, monoclonal antibodies and antiangiogenic agents.

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“…Pan-HDAC and class Iselective inhibitors, currently undergoing clinical trials, alter physiological functions that require protein deacetylation [20,49]. There are currently two HDAC inhibitors, SAHA (pan-HDACi) and FK228 (selective-class I HDACi), approved by the FDA for the treatment of cutaneous T cell lymphoma (CTCL).…”

Section: Hdacs and Autoimmunitymentioning

confidence: 99%

“…Due to the large number of HDACs that are targeted, pan-HDAC inhibitors have been associated with deleterious side effects during clinical trials including fatigue, nausea, thrombocytopenia, and electrocardiograph abnormalities [20,21]. For this reason, a more targeted approach is warranted if HDAC inhibitors are to be used in the treatment of autoimmune disease.…”

Section: Introductionmentioning

confidence: 99%

Isoform-Selective HDAC Inhibition in Autoimmune DiseaseNicole L Regna1* and Christopher M Reilly2

Regna

Reilly²

2014

J Clin Cell Immunol

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Histone deacetylases are a class of enzymes that play an important role in protein modification and cellular function. Ongoing research suggests that HDAC inhibitors may be efficacious in the treatment of a wide range of diseases from cancer to autoimmune disease. HDACi therapy has shown promising results both in vitro and in vivo for the treatment of autoimmune disease. To date, 18 isoforms of HDACs have been identified, which exist in four different classes: class I (HDAC1, 2, 3, and 8), class II (HDAC4, 5, 6, 7, 9, and 10) class III (sirtuins1-7), and class IV (HDAC11). The mechanism of action through which HDACs function remains to be fully elucidated. However, the use of isoform-selective HDAC inhibitors has been helpful in determining the physiological role of individual HDACs as well as in decreasing the toxicity of HDACi therapy. This review will focus on isoform-selective HDACs and how they may be effective for the treatment of autoimmune disease.

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Targeted Cancer Therapy: Giving Histone Deacetylase Inhibitors All They Need To Succeed

Cited by 334 publications

References 139 publications

Histone deacetylase inhibitors in cancer therapy. A review

Histone deacetylase inhibitors in cancer therapy. A review

Endpoint of Cancer Treatment: Targeted Therapies

Isoform-Selective HDAC Inhibition in Autoimmune DiseaseNicole L Regna1* and Christopher M Reilly2

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