Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer

Fukumoto, Takeshi; Park, Pyoung Hwa; Wu, Shuai; Fatkhutdinov, Nail; Karakashev, Sergey; Nacarelli, Timothy; Kossenkov, Andrew V.; Speicher, David W.; Jean, Stéphanie; Zhang, Lin; Wang, Tian Li; Shih, Ie Ming; Conejo-Garcia, José R.; Bitler, Benjamin G.; Zhang, Rugang

doi:10.1016/j.celrep.2018.03.019

Cited by 84 publications

(72 citation statements)

References 24 publications

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“…SIRT2 binds and deacetylates PR-Set7/SET8/KMT5A at K90, and increases the H4K20me1 level (Serrano et al, 2013). HDACs also interact with polycomb-group (PcG) proteins to reset chromatin remodeling and transcriptional repression (Van Der Vlag and Otte, 1999;Kuzmichev et al, 2005;Zhang et al, 2012b;Fukumoto et al, 2018). SIRT1 interacts with Set7/9 (also called KMT7), with several sites being methylated by Set7/9.…”

Section: Synergetic Regulation Of Hdacs and Other Histone Modifiersmentioning

confidence: 99%

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Guo

Tian

Zhu

2020

Front. Cell Dev. Biol.

199

135

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Genetic mutations and abnormal gene regulation are key mechanisms underlying tumorigenesis. Nucleosomes, which consist of DNA wrapped around histone cores, represent the basic units of chromatin. The fifth amino group (N ε) of histone lysine residues is a common site for post-translational modifications (PTMs), and of these, acetylation is the second most common. Histone acetylation is modulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), and is involved in the regulation of gene expression. Over the past two decades, numerous studies characterizing HDACs and HDAC inhibitors (HDACi) have provided novel and exciting insights concerning their underlying biological mechanisms and potential anti-cancer treatments. In this review, we detail the diverse structures of HDACs and their underlying biological functions, including transcriptional regulation, metabolism, angiogenesis, DNA damage response, cell cycle, apoptosis, protein degradation, immunity and other several physiological processes. We also highlight potential avenues to use HDACi as novel, precision cancer treatments.

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Section: Synergetic Regulation Of Hdacs and Other Histone Modifiersmentioning

confidence: 99%

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Guo

Tian

Zhu

2020

Front. Cell Dev. Biol.

199

135

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“…These findings indicate that targeting PRC2 activity in SWI/SNF mutant cancers may provide an effective means to treat this large cohort of patients. Finally, targeting HDAC activity, particularly HDAC2, blocks the progression of Arid1a mutant ovarian cancer cells (Fukumoto et al 2018). Thus, NuRD complexes, harboring HDAC1/2, may also be relevant in SWI/SNF mutant cancers.…”

Section: Therapeutic Opportunities: Restoring or Tipping The Chromatimentioning

confidence: 99%

Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer

2019

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Changes in chromatin structure mediated by ATP-dependent nucleosome remodelers and histone modifying enzymes are integral to the process of gene regulation. Here, we review the roles of the SWI/SNF (switch/sucrose nonfermenting) and NuRD (nucleosome remodeling and deacetylase) and the Polycomb system in chromatin regulation and cancer. First, we discuss the basic molecular mechanism of nucleosome remodeling, and how this controls gene transcription. Next, we provide an overview of the functional organization and biochemical activities of SWI/SNF, NuRD, and Polycomb complexes. We describe how, in metazoans, the balance of these activities is central to the proper regulation of gene expression and cellular identity during development. Whereas SWI/SNF counteracts Polycomb, NuRD facilitates Polycomb repression on chromatin. Finally, we discuss how disruptions of this regulatory equilibrium contribute to oncogenesis, and how new insights into the biological functions of remodelers and Polycombs are opening avenues for therapeutic interventions on a broad range of cancer types.

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“…The above genes with high frequency of mutations may be potential drug targets for precision treatment of BL. For examples, cyclophosphamide, fludarabine and mycophenolate mofetil could be used for BL cases with TCF3 mutations or TP53 mutations [ 34 ], while histone deacetylase inhibitors (HDACi) [ 35 , 36 ] might be helpful for cases with CREBBP or ARID1A mutations.…”

Section: Discussionmentioning

confidence: 99%

Identification of clinical molecular targets for childhood Burkitt lymphoma

Zhang

Meng

Jiang³

et al. 2020

Translational Oncology

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Burkitt lymphoma (BL) is a malignant tumor in children. Although BL is generally curable, early relapse and refractoriness may occur. Some molecular indicators have been recently suggested for BL diagnosis, but large heterogeneity still exists. This study aimed at providing clinical molecular targets and methods that may help improve diagnosis and treatment of childhood BL. Only children patients were included in the study, and targeted gene sequencing was conducted to identify tumor specific mutations. The mRNA and protein level expression of potential target genes were measured by real-time PCR and immunohistochemistry. The relationship between BL specific gene mutation and differential expression with clinical features was analyzed. The results showed that i) detailed analysis of c-MYC / BCL2 / BCL6 gene loci alteration and gene expression would help in accurate diagnosis and treatment determination of childhood BL; ii) loss-of-function mutations in SOCS1 or CIITA gene might be used as malignant markers for BL diagnosis and prognosis; iii) specific mutations of CD79A , MYD88 , KLF2 , DNMT3A and NFKBIE genes often concurrently existed in BL and showed association with benign clinical outcomes; iv) the high expression of MYC , TCF3 and loss-of-function ID3 genes in tumor may be potential therapeutic targets and could be used for treatment monitoring; and v) four MYC -translocation negative cases were re-defined as high-grade B-cell lymphoma-not otherwise specified (HGBL-NOS) but showed similar clinical outcomes and molecular features to other BL cases in the study, suggesting more studies needed to explore the molecular mechanisms and clinical significance of this provisional tumor entity.

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Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer

Cited by 84 publications

References 24 publications

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Dangerous liaisons: interplay between SWI/SNF, NuRD, and Polycomb in chromatin regulation and cancer

Identification of clinical molecular targets for childhood Burkitt lymphoma

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