Histone Deacetylase Inhibitors Downregulate Checkpoint Kinase 1 Expression to Induce Cell Death in Non-Small Cell Lung Cancer Cells

Brazelle, William; Kreahling, Jenny; Gemmer, Jennifer; Ma, Yihong; Cress, W. Douglas; Haura, Eric B.; Altiok, Soner

doi:10.1371/journal.pone.0014335

Cited by 65 publications

(56 citation statements)

References 38 publications

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“…To confirm that loss of ING2 did lead to gene repression, we validated some target genes with real-time PCR. We chose to focus on CDC2 because it is a master regulator of G2/M phase cell cycle progression and its protein levels are known to be reduced by HDAC inhibitors in some cell lines (44). We found that CDC2 was consistently down-regulated in ING2 knockdown cells and repressed by SAHA treatment (Fig.…”

Section: Fig 3 Saha-induced Differential Network Analysismentioning

confidence: 99%

Suberoylanilide Hydroxamic Acid (SAHA)-Induced Dynamics of a Human Histone Deacetylase Protein Interaction Network

Sardiu

Smith

Groppe

et al. 2014

Molecular & Cellular Proteomics

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Section: Fig 3 Saha-induced Differential Network Analysismentioning

confidence: 99%

Suberoylanilide Hydroxamic Acid (SAHA)-Induced Dynamics of a Human Histone Deacetylase Protein Interaction Network

Sardiu

Smith

Groppe

et al. 2014

Molecular & Cellular Proteomics

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“…Histone deacetylase (HDAC) modulates the transcription rate and the protein levels of several components of the DNAdamage response cascade [109][110][111][112][113][114]. Heat-shock protein 90 (HSP90) chaperones "client" proteins into their native conformations, regulating multiple aspects of protein function.…”

Section: Heat Shock Protein 90 and Histone Deacetylase Inhibitorsmentioning

confidence: 99%

Biology and Management of Patients With Triple-Negative Breast Cancer

2016

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Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared with other breast cancer subtypes. Because of the lack of approved targeted therapy, at present chemotherapy remains the mainstay of treatment for early and advanced disease. TNBC is enriched for germline BRCA mutation, providing a foundation for the use of this as a biomarker to identify patients suitable for treatment with DNA-damaging agents. Inherited and acquired defects in homologous recombination DNA repair, a phenotype termed "BRCAness," may be present in a large proportion of TNBC cases, making it an attractive selection and response biomarker for DNAdamaging therapy. Triple-negative breast cancer is a diverse entity for which additional subclassifications are needed.Increasing understanding of biologic heterogeneity of TNBC has provided insight into identifying potentially effective systemic therapies, including cytotoxic and targeted agents. Numerous experimental approaches are under way, and several encouraging drug classes, such as immune checkpoint inhibitors, poly(ADP-ribose) polymerase inhibitors, platinum agents, phosphatidylinositol-3-kinase pathway inhibitors, and androgen receptor inhibitors, are being investigated in TNBC. Molecular biomarker-based patient selection in early-phase trials has the potential to accelerate development of effective therapies for this aggressive breast cancer subtype. TNBC is a complex disease, and it is likely that several different targeted approaches will be needed to make meaningful strides in improving the outcomes. The Oncologist 2016;21:1050-1062Implications for Practice: Triple-negative breast cancer (TNBC) is an aggressive subtype that is associated with poor outcomes.This article reviews clinical features and discusses the molecular diversity of this unique subtype. Current treatment paradigms, the role ofgermline testing, and platinum agents in TNBC are reviewed. Results and observations from pertinent clinical trials with potential implications for patient management are summarized.This article also discusses the clinical development and ongoing clinical trials of novel promising therapeutic agents in TNBC.

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“…Increased accessibility to DNA-damaging agents, however, is unlikely to be the only mechanism responsible for the effects of treatment with HDAC inhibitors. HDACs have also been shown to regulate the transcription rate and the protein levels of several components of the DDR cascade (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

Section: Hdac Inhibitors and The Dna Damage Responsementioning

confidence: 99%

Molecular Pathways: Old Drugs Define New Pathways: Non-Histone Acetylation at the Crossroads of the DNA Damage Response and Autophagy

Botrugno

Robert

Vanoli

et al. 2012

Clinical Cancer Research

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Histone deacetylases (HDAC) modulate acetylation and the function of histone and non-histone proteins. HDAC inhibitors have been developed to block the aberrant action of HDACs in cancer, and several are in clinical use (vorinostat, romidepsin, and valproic acid). Detailed understanding of their action is lacking, however, and their clinical activity is limited in most cases. Recently, HDACs have been involved in the control of the DNA damage response (DDR) at several levels and in directly regulating the acetylation of a number of DDR proteins (including CtIP and Exo1). Mechanistically, acetylation leads to the degradation of double-strand break repair enzymes through autophagy, providing a novel, direct link between DDR and autophagy. These observations, obtained in yeast cells, should now be translated to mammalian model systems and cancer cells to reveal whether this acetylation link is maintained in mammals, and if and how it is deregulated in cancer. In addition to HDACs, DDR and autophagy have been addressed pharmacologically, suggesting that the acetylation link, if involved in cancer, can be exploited for the design of new anticancer treatments. Clin Cancer Res; 18(9); 2436-42. Ó2012 AACR.

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Histone Deacetylase Inhibitors Downregulate Checkpoint Kinase 1 Expression to Induce Cell Death in Non-Small Cell Lung Cancer Cells

Cited by 65 publications

References 38 publications

Suberoylanilide Hydroxamic Acid (SAHA)-Induced Dynamics of a Human Histone Deacetylase Protein Interaction Network

Suberoylanilide Hydroxamic Acid (SAHA)-Induced Dynamics of a Human Histone Deacetylase Protein Interaction Network

Biology and Management of Patients With Triple-Negative Breast Cancer

Molecular Pathways: Old Drugs Define New Pathways: Non-Histone Acetylation at the Crossroads of the DNA Damage Response and Autophagy

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