Epigenetic Pathways Offer Targets for Ovarian Cancer Treatment

Gyparaki, Melina-Theoni; Papavassiliou, Athanasios G.

doi:10.1016/j.clbc.2017.09.009

Cited by 8 publications

(4 citation statements)

References 30 publications

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“…These modifications on histone residues include acetylation, methylation, phosphorylation, ubiquitination, sumoylation, ADP‐ribosylation, deimination, proline isomerization, and the newly identified propionylation (Sawan & Herceg, ). These reversible changes can result in activation or inactivation of chromatin and normally occur in cells via modification of the enzymes (Chervona & Costa, ; Gyparaki & Papavassiliou, ). Deregulation of histone modification may affect gene expression, cellular processes and lead to malignant outcomes (Sawan & Herceg, ).…”

Section: Epigeneticsmentioning

confidence: 99%

Molecular mechanisms of drug resistance in ovarian cancer

Norouzi-Barough

Sarookhani

Sharifi

et al. 2018

Journal Cellular Physiology

157

128

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Ovarian cancer is the most lethal malignancy among the gynecological cancers, with a 5-year survival rate, mainly due to being diagnosed at advanced stages, recurrence and resistance to the current chemotherapeutic agents. Drug resistance is a complex phenomenon and the number of known involved genes and cross-talks between signaling pathways in this process is growing rapidly. Thus, discovering and understanding the underlying molecular mechanisms involved in chemo-resistance are crucial for management of treatment and identifying novel and effective drug targets as well as drug discovery to improve therapeutic outcomes. In this review, the major and recently identified molecular mechanisms of drug resistance in ovarian cancer from relevant literature have been investigated. In the final section of the paper, new approaches for studying detailed mechanisms of chemo-resistance have been briefly discussed.

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Section: Epigeneticsmentioning

confidence: 99%

Molecular mechanisms of drug resistance in ovarian cancer

Norouzi-Barough

Sarookhani

Sharifi

et al. 2018

Journal Cellular Physiology

157

128

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“…As chemotherapy of ovarian cancer is mainly target non-specific, and because epigenetic modifications possibly play similar types of roles in ovarian and breast cancers, current investigators are extremely encouraged to develop epigenetic therapies in combination with traditional drugs for breast and ovarian cancers. [ 50 , 61 , 62 , 91 , 92 , 94 , 96 , 97 , 98 , 99 ].…”

Section: Drug Resistancementioning

confidence: 99%

A Comparative Analysis of Genetic and Epigenetic Events of Breast and Ovarian Cancer Related to Tumorigenesis

Longacre

Snyder

Housman

et al. 2016

IJMS

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Breast cancer persists as the most common cause of cancer death in women worldwide. Ovarian cancer is also a significant source of morbidity and mortality, as the fifth leading cause of cancer death among women. This reflects the continued need for further understanding and innovation in cancer treatment. Though breast and ovarian cancer usually present as distinct clinical entities, the recent explosion of large-scale -omics research has uncovered many overlaps, particularly with respect to genetic and epigenetic alterations. We compared genetic, microenvironmental, stromal, and epigenetic changes common between breast and ovarian cancer cells, as well as the clinical relevance of these changes. Some of the most striking commonalities include genetic alterations of BRCA1 and 2, TP53, RB1, NF1, FAT3, MYC, PTEN, and PIK3CA; down regulation of miRNAs 9, 100, 125a, 125b, and 214; and epigenetic alterations such as H3K27me3, H3K9me2, H3K9me3, H4K20me3, and H3K4me. These parallels suggest shared features of pathogenesis. Furthermore, preliminary evidence suggests a shared epigenetic mechanism of oncogenesis. These similarities, warrant further investigation in order to ultimately inform development of more effective chemotherapeutics, as well as strategies to circumvent drug resistance.

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“…Epigenetic gene regulation is one of the mechanisms that regulate treatment response. For example, whole genome DNA methylation analysis found that epigenetic regulation of potentially clinically relevant genes predicts response to platinum [57][58][59] . Also, lncRNAs have been associated with epigenetic regulation of HGSC 60 , and specific lncRNAs have been associated with chemo-resistance 61 .…”

Section: Discussionmentioning

confidence: 99%

Creation and validation of models to predict response to primary treatment in serous ovarian cancer

Bosquet

Devor

Newtson

et al. 2021

Sci Rep

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Nearly a third of patients with high-grade serous ovarian cancer (HGSC) do not respond to initial therapy and have an overall poor prognosis. However, there are no validated tools that accurately predict which patients will not respond. Our objective is to create and validate accurate models of prediction for treatment response in HGSC. This is a retrospective case–control study that integrates comprehensive clinical and genomic data from 88 patients with HGSC from a single institution. Responders were those patients with a progression-free survival of at least 6 months after treatment. Only patients with complete clinical information and frozen specimen at surgery were included. Gene, miRNA, exon, and long non-coding RNA (lncRNA) expression, gene copy number, genomic variation, and fusion-gene determination were extracted from RNA-sequencing data. DNA methylation analysis was performed. Initial selection of informative variables was performed with univariate ANOVA with cross-validation. Significant variables (p < 0.05) were included in multivariate lasso regression prediction models. Initial models included only one variable. Variables were then combined to create complex models. Model performance was measured with area under the curve (AUC). Validation of all models was performed using TCGA HGSC database. By integrating clinical and genomic variables, we achieved prediction performances of over 95% in AUC. Most performances in the validation set did not differ from the training set. Models with DNA methylation or lncRNA underperformed in the validation set. Integrating comprehensive clinical and genomic data from patients with HGSC results in accurate and robust prediction models of treatment response.

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Epigenetic Pathways Offer Targets for Ovarian Cancer Treatment

Cited by 8 publications

References 30 publications

Molecular mechanisms of drug resistance in ovarian cancer

Molecular mechanisms of drug resistance in ovarian cancer

A Comparative Analysis of Genetic and Epigenetic Events of Breast and Ovarian Cancer Related to Tumorigenesis

Creation and validation of models to predict response to primary treatment in serous ovarian cancer

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