Epigenomic-Based Diagnostic Techniques and Therapeutic Strategies for Ovarian Cancer
Introduction. High rate of mortality associated with epithelial ovarian cancer is due to the tumor recurrence and resistance to multiple drugs after good initial response to the standard chemotherapy with drugs such as platinum/taxanes1. This occurs in a majority of post-menopausal women aged 55-74 years with the etiology of ovarian malignancies is related to the hormonal imbalance2. Three epigenetic mechanisms used for ovarian cancer are DNA methylation, histone modifications, and chromatin remodeling. There is also the use of LncRNAs with more than 200 bp used in post-translational histone modifications. They will bind to different chromatin-modifying proteins or bring other protein complexes into the proximity3. Methods. Simultaneous analysis of multiple genes’ methylation status in blood-based tests may increase the sensitivity and specificity for further classification of ovarian cancers at the molecular level3. Another study involving microarray-based analysis identified 112 methylated loci significant for evaluating survival in patients without the progression of the cancer and also the prognosis of the patients4. Results. A high rate of promoter hypermethylation was identified in at least of the six genes (BRCA1, RASSF1A, APC, p14ARF, p16INK4A and DAPK)4. Cell adaptation to HDAC inhibitor-mediated epigenomic disruption has been frequently observed5. Recent identification of large miRNA and LncRNA classes as epigenetic regulators of gene expression granted new opportunities for miRNA and LncRNA-employed prognostic evaluation and targeting of EOC6. Conclusions. Seventy percent of the cases are diagnosed at an advanced stage and the need for good diagnostic measures and treatments are important. The use of mRNAs and LncRNAs in disease progression is the target. Focus is on inhibition of aberrant methylation and use of DNAm profiling. Hypermethylation of microarray-based analysis were identified 112 methylated loci. The main target is on novel small-molecule DNA methyltransferase inhibitor guadecitabine and histone deacetylase inhibitors7.
- Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review. Cancer Biol Med. 2017;14(1):9–32. doi:10.20892/j.issn.2095-3941.2016.0084
- Jonathan G Bijron, Guus M Bol, Rene HM Verheijen & Paul J van Diest (Professor and Head) (2012)Epigenetic biomarkers in the diagnosis of ovarian cancer, Expert Opinion on Medical Diagnostics, 6:5,421-438, DOI: 1517/17530059.2012.702105
- Zhan L, Li J, Wei B. Long non-coding RNAs in ovarian cancer. J Exp Clin Cancer Res. 2018;37(1):120. Published 2018 Jun 19. doi:10.1186/s13046-018-0793-4
- Koukoura, O., Spandidos, D.A., Daponte, A., & Sifakis, S. (2014). DNA methylation profiles in ovarian cancer: Implication in diagnosis and therapy (Review). Molecular Medicine Reports, 10, 3-9. https://doi.org/10.3892/mmr.2014.2221
- Klymenko Y, Nephew KP. Epigenetic Crosstalk between the Tumor Microenvironment and Ovarian Cancer Cells: A Therapeutic Road Less Traveled. Cancers (Basel). 2018;10(9):295. Published 2018 Aug 30. doi:10.3390/cancers10090295
- Earp MA, Cunningham JM. DNA methylation changes in epithelial ovarian cancer histotypes. Genomics. 2015;106(6):311–321. doi:10.1016/j.ygeno.2015.09.001
- Fang F, Munck J, Tang J, Taverna P, Wang Y, Miller DF, Pilrose J, Choy G, Azab M, Pawelczak KS, et al. The novel, small-molecule DNA methylation inhibitor SGI-110 as an ovarian cancer chemosensitizer. Clin Cancer Res. 2014;20(24):6504–6516. doi: 10.1158/1078-0432.CCR-14-1553.