Cancer Treatment: An Epigenetic View

Aydin, Cansu; Kalkan, Rasime

doi:10.1055/s-0040-1713610

Cited by 4 publications

(3 citation statements)

References 49 publications

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“…Indeed, an increasing number of small molecules are being developed to inhibit the deposition of chromatin marks, the elimination of these marks and the interactions of chromatin modifiers and transcriptional regulators with these marks. These new families of compounds are collectively named "epidrugs", and are showing a great potential for cancer treatment [199,200]. Interestingly, numerous compounds originally designed for other indications, and that failed to prosper towards their original clinical applications, are being repurposed as promising epidrugs for cancer therapy [201].…”

Section: Perspective On Application In Therapymentioning

confidence: 99%

Epigenetic remodelling in human hepatocellular carcinoma

Braghini

Romito

et al. 2022

J Exp Clin Cancer Res

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Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, being the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death. As other heterogeneous solid tumours, HCC results from a unique synergistic combination of genetic alterations mixed with epigenetic modifications.In HCC the patterns and frequencies of somatic variations change depending on the nearby chromatin. On the other hand, epigenetic alterations often induce genomic instability prone to mutations. Epigenetics refers to heritable states of gene expression without alteration to the DNA sequence itself and, unlike genetic changes, the epigenetic modifications are reversible and affect gene expression more extensively than genetic changes. Thus, studies of epigenetic regulation and the involved molecular machinery are greatly contributing to the understanding of the mechanisms that underline HCC onset and heterogeneity. Moreover, this knowledge may help to identify biomarkers for HCC diagnosis and prognosis, as well as future new targets for more efficacious therapeutic approaches.In this comprehensive review we will discuss the state-of-the-art knowledge about the epigenetic landscape in hepatocarcinogenesis, including evidence on the diagnostic and prognostic role of non-coding RNAs, modifications occurring at the chromatin level, and their role in the era of precision medicine.Apart from other better-known risk factors that predispose to the development of HCC, characterization of the epigenetic remodelling that occurs during hepatocarcinogenesis could open the way to the identification of personalized biomarkers. It may also enable a more accurate diagnosis and stratification of patients, and the discovery of new targets for more efficient therapeutic approaches.

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Section: Perspective On Application In Therapymentioning

confidence: 99%

Epigenetic remodelling in human hepatocellular carcinoma

Braghini

Romito

et al. 2022

J Exp Clin Cancer Res

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“…Epigenetic modifications refer to covalent modifications to either histone molecules or DNA that are heritable, reversible, and do not alter the DNA sequence. A growing number of studies have highlighted the importance of epigenetic changes in cancer treatment and prognosis [ 9 ]. Currently, nine epigenetic agents are available in the US for treating cancer, including two DNA methyltransferase (DNMT) inhibitors (azacitidine and decitabine), four histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin, belinostat, and panobinostat), two isocitrate dehydrogenase inhibitors (enasidenib and ivosidenib), and one EZH2 inhibitor (tazemetostatv) [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting the LSD1-G9a-ER Stress Pathway as a Novel Therapeutic Strategy for Esophageal Squamous Cell Carcinoma

et al. 2022

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Despite recent advances in the management and treatment of esophageal squamous cell carcinoma (ESCC), the prognosis remains extremely poor, and current nonsurgical treatment options are limited. To identify new therapeutic targets, we screened a curated library of epigenetic compounds using a panel of cancer cell lines and found that coinhibiting the histone demethylase LSD1 and the histone methyltransferase G9a potently suppresses cell growth; similar results were obtained by knocking down both LSD1 and G9a expression. Importantly, we also found that inhibiting LSD1 and G9a significantly decreased tumor growth in a xenograft mouse model with ESCC cell lines. To examine the clinical relevance of these findings, we performed immunohistochemical analyses of microarray profiling data obtained from human esophageal squamous cancer tissues and found that both LSD1 and G9a are upregulated in cancer tissues compared to healthy tissues, and this increased expression was significantly correlated with poor prognosis. Mechanistically, we discovered that inhibiting LSD1 and G9a induces cell death via S-phase arrest and apoptosis, and cotargeting ER stress pathways increased this effect both in vitro and in vivo. Taken together, these findings provide compelling evidence that targeting LSD1, G9a, and ER stress-related pathways may serve as a viable therapeutic strategy for ESCC.

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“…Recent evidence suggests that epigenetic changes in speci c genes may mediate carcinogenesis or predict prognosis (11). DNA methylation is a hot research of epigenetic changes in cervical cancer, and either hypomethylation or hypermethylation is a key event in carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Significance of MAFK and its Methylation in Cervical Cancer

Zhang

Liu

et al. 2021

Preprint

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Background: The purpose of this study was to determine the value of MAFK as a biomarker of cervical cancer prognosis and to explore its methylation and possible cellular signaling pathways. Methods: We analyzed the cervical cancer data of The Cancer Genome Atlas (TCGA) through bioinformatics, including MAFK expression, methylation, prognosis and genome enrichment analysis. Results: MAFK expression was higher in cervical cancer tissues and was negatively correlated with the methylation levels of five CpG sites. MAFK is an independent prognostic factor of cervical cancer and is involved in the Nod-like receptor signaling pathway. CMap analysis screened four drug candidates for cervical cancer treatment. Conclusions: We confirmed that MAFK is a novel prognostic biomarker for cervical cancer and aberrant methylation may also affect MAFK expression and carcinogenesis. This study provides a new molecular target for the prognostic evaluation and treatment of cervical cancer.

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Cancer Treatment: An Epigenetic View

Cited by 4 publications

References 49 publications

Epigenetic remodelling in human hepatocellular carcinoma

Epigenetic remodelling in human hepatocellular carcinoma

Targeting the LSD1-G9a-ER Stress Pathway as a Novel Therapeutic Strategy for Esophageal Squamous Cell Carcinoma

The Prognostic Significance of MAFK and its Methylation in Cervical Cancer

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