Cancer Treatment: An Epigenetic View

AbstractCancer can be identified as an uncontrolled growth and reproduction of cell. Accumulation of genetic aberrations (mutations of oncogenes and tumor-suppressor genes and epigenetic modifications) is one of the characteristics of cancer cell. Increasing number of studies highlighted importance of the epigenetic alterations in cancer treatment and prognosis. Now, cancer epigenetics have a huge importance for developing novel biomarkers and therapeutic target for cancer. In this review, we will provide a summary of the major epigenetic changes involved in cancer and preclinical results of epigenetic therapeutics.

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Methyl-CpG-binding proteins in cancer: blaming the DNA methylation messenger

Biochemistry and Cell Biology ◽

10.1139/o05-035 ◽

2005 ◽

Vol 83 (3) ◽

pp. 374-384 ◽

Cited By ~ 42

Author(s):

Esteban Ballestar ◽

Manel Esteller

Keyword(s):

Dna Methylation ◽

Tumor Suppressor Genes ◽

Binding Proteins ◽

Excision Repair ◽

Cpg Islands ◽

Current Data ◽

Epigenetic Alterations ◽

Domain Family ◽

Promoter Regions ◽

Cancer Epigenetics

In recent years, epigenetic alterations have come to prominence in cancer research. In particular, hypermethylation of CpG islands located in the promoter regions of tumor-suppressor genes is now firmly established as an important mechanism for gene inactivation in cancer. One of the most remarkable achievements in the field has been the identification of the methyl-CpG-binding domain family of proteins, which provide mechanistic links between specific patterns of DNA methylation and histone modifications. Although many of the current data indicate that methyl-CpG-binding proteins play a key role in maintaining a transcriptionally inactive state of methylated genes, MBD4 is also known to be involved in excision repair of T:G mismatches. The latter is a member of this family of proteins and appears to play a role in reducing mutations at 5-methylcytosine. This review examines the contribution of methyl-CpG-binding proteins in the epigenetic pathway of cancer.Key words: methyl-CpG-binding, MeCP2, DNA methylation, Rett syndrome, cancer epigenetics.

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Gene duplication, rather than epigenetic changes, drives FGF4 overexpression in KIT/PDGFRA/SDH/RAS-P WT GIST

Scientific Reports ◽

10.1038/s41598-020-76519-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Milena Urbini ◽

Annalisa Astolfi ◽

Valentina Indio ◽

Margherita Nannini ◽

Angela Schipani ◽

...

Keyword(s):

Therapeutic Target ◽

Molecular Mechanisms ◽

Genomic Structure ◽

Epigenetic Mechanism ◽

Epigenetic Changes ◽

Epigenetic Alterations ◽

Wild Type ◽

Gastrointestinal Stromal Tumours ◽

Super Enhancer ◽

First Time

AbstractGastrointestinal stromal tumours that are wild type for KIT and PDGFRA are referred to as WT GISTs. Of these tumours, SDH-deficient (characterized by the loss of SDHB) and quadruple WT GIST (KIT/PDGFRA/SDH/RAS-P WT) subgroups were reported to display a marked overexpression of FGF4, identifying a putative common therapeutic target for the first time. In SDH-deficient GISTs, methylation of an FGF insulator region was found to be responsible for the induction of FGF4 expression. In quadruple WT, recurrent focal duplication of FGF3/FGF4 was reported; however, how it induced FGF4 expression was not investigated. To assess whether overexpression of FGF4 in quadruple WT could be driven by similar epigenetic mechanisms as in SDH-deficient GISTs, we performed global and locus-specific (on FGF4 and FGF insulator) methylation analyses. However, no epigenetic alterations were detected. Conversely, we demonstrated that in quadruple WT GISTs, FGF4 expression and the structure of the duplication were intimately connected, with the copy of FGF4 closer to the ANO1 super-enhancer being preferentially expressed. In conclusion, we demonstrated that in quadruple WT GISTs, FGF4 overexpression is not due to an epigenetic mechanism but rather to the specific genomic structure of the duplication. Even if FGF4 overexpression is driven by different molecular mechanisms, these findings support an increasing biologic relevance of the FGFR pathway in WT GISTs, both in SDH-deficient and quadruple WT GISTs, suggesting that it may be a common therapeutic target.

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174 POSTER Epigenetic changes of tumor suppressor genes and therapeutic implications in glioblastoma

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(08)72106-2 ◽

2008 ◽

Vol 6 (12) ◽

pp. 55-56

Author(s):

L. Sooman ◽

J. Gullbo ◽

J. Lennartsson ◽

S. Bergström ◽

E. Blomquist ◽

...

Keyword(s):

Tumor Suppressor ◽

Tumor Suppressor Genes ◽

Epigenetic Changes ◽

Suppressor Genes ◽

Therapeutic Implications

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The role of clusterin in prostate cancer: treatment resistance and potential as a therapeutic target

Expert Review of Anticancer Therapy ◽

10.1586/14737140.2015.1064769 ◽

2015 ◽

Vol 15 (9) ◽

pp. 1049-1061 ◽

Cited By ~ 16

Author(s):

Lateef A Muhammad ◽

Fred Saad

Keyword(s):

Prostate Cancer ◽

Cancer Treatment ◽

Therapeutic Target ◽

Treatment Resistance ◽

Prostate Cancer Treatment

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Modification of Epigenetic Histone Acetylation in Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers10010008 ◽

2018 ◽

Vol 10 (1) ◽

pp. 8 ◽

Cited By ~ 22

Author(s):

Kwei-Yan Liu ◽

Li-Ting Wang ◽

Shih-Hsien Hsu

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Suppressor ◽

Tumor Suppressor Genes ◽

Chemical Sensor ◽

Enzyme Level ◽

Tumor Therapy ◽

Tumor Formation ◽

Current Evidence ◽

Epigenetic Changes ◽

Suppressor Genes

Cells respond to various environmental factors such as nutrients, food intake, and drugs or toxins by undergoing dynamic epigenetic changes. An imbalance in dynamic epigenetic changes is one of the major causes of disease, oncogenic activities, and immunosuppressive effects. The aryl hydrocarbon receptor (AHR) is a unique cellular chemical sensor present in most organs, and its dysregulation has been demonstrated in multiple stages of tumor progression in humans and experimental models; however, the effects of the pathogenic mechanisms of AHR on epigenetic regulation remain unclear. Apart from proto-oncogene activation, epigenetic repressions of tumor suppressor genes are involved in tumor initiation, procession, and metastasis. Reverse epigenetic repression of the tumor suppressor genes by epigenetic enzyme activity inhibition and epigenetic enzyme level manipulation is a potential path for tumor therapy. Current evidence and our recent work on deacetylation of histones on tumor-suppressive genes suggest that histone deacetylase (HDAC) is involved in tumor formation and progression, and treating hepatocellular carcinoma with HDAC inhibitors can, at least partially, repress tumor proliferation and transformation by recusing the expression of tumor-suppressive genes such as TP53 and RB1.

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Could GLUT12 be a Potential Therapeutic Target in Cancer Treatment? A Preliminary Report

Journal of Cancer ◽

10.7150/jca.10429 ◽

2015 ◽

Vol 6 (2) ◽

pp. 139-143 ◽

Cited By ~ 12

Author(s):

Jonai Pujol-Gimenez ◽

Fátima Pérez de Heredia ◽

Miguel Angel Idoate ◽

Rachel Airley ◽

María Pilar Lostao ◽

...

Keyword(s):

Cancer Treatment ◽

Therapeutic Target ◽

Preliminary Report ◽

Potential Therapeutic Target

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Genetic and Epigenetic Aspects of Atopic Dermatitis

International Journal of Molecular Sciences ◽

10.3390/ijms21186484 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6484 ◽

Cited By ~ 1

Author(s):

Bogusław Nedoszytko ◽

Edyta Reszka ◽

Danuta Gutowska-Owsiak ◽

Magdalena Trzeciak ◽

Magdalena Lange ◽

...

Keyword(s):

Atopic Dermatitis ◽

Treatment Strategies ◽

Structural Proteins ◽

Epigenetic Changes ◽

Epigenetic Alterations ◽

Adaptive Immune ◽

Genes Encoding ◽

Inflammatory Processes ◽

Non Coding Rnas

Atopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications are mainly mediated by DNA methylation, histone acetylation, and the action of specific non-coding RNAs. It has been documented that the profile of epigenetic changes in patients with atopic dermatitis (AD) differs from that observed in healthy people. This applies to the genes affecting the regulation of immune response and inflammatory processes, e.g., both affecting Th1 bias and promoting Th2 responses and the genes of innate immunity, as well as those encoding the structural proteins of the epidermis. Understanding of the epigenetic alterations is therefore pivotal to both create new molecular classifications of atopic dermatitis and to enable the development of personalized treatment strategies.

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