Ovarian cancer: epigenetics, drug resistance, and progression

Abstract

Ovarian cancer (OC) is one of the most common malignant tumors in women. OC is associated with the activation of oncogenes, the inactivation of tumor suppressor genes, and the activation of abnormal cell signaling pathways. Moreover, epigenetic processes have been found to play an important role in OC tumorigenesis. Epigenetic processes do not change DNA sequences but regulate gene expression through DNA methylation, histone modification, and non-coding RNA. This review comprehensively considers the importance of epigenetics in OC, with a focus on microRNA and long non-coding RNA. These types of RNA are promising molecular markers and therapeutic targets that may support precision medicine in OC. DNA methylation inhibitors and histone deacetylase inhibitors may be useful for such targeting, with a possible novel approach combining these two therapies. Currently, the clinical application of such epigenetic approaches is limited by multiple obstacles, including the heterogeneity of OC, insufficient sample sizes in reported studies, and non-optimized methods for detecting potential tumor markers. Nonetheless, the application of epigenetic approaches to OC patient diagnosis, treatment, and prognosis is a promising area for future clinical investigation.

Integration of Genomic Profiling and Organoid Development in Precision Oncology

“…Ovarian cancer is one of the most malignant and fatal gynecological tumors. High-grade serous ovarian cancer (HGSOC) is a critical histological type of ovarian cancer [ 2 , 28 , 29 ]. Germline mutations in BRCA1 and BRCA2 , which are reported in 10–15% of ovarian cancers, play an essential role as genetic risk factors for cancer development [ 30 ].…”

“…In addition, BRCA1 mutations are strongly associated with poor clinical outcomes in HGSOC patients [ 31 , 32 ]. In 2011, The Cancer Genome Atlas (TCGA), using NGS and microarray data analyzed from HGSOC patients, revealed four subtypes of HGSOC based on gene expression: mesenchymal, immune response, proliferation, and differentiation [ 2 , 33 ]. Using NGS data, Murakami et al established a genetically consistent histopathological classification system for HGSOC.…”

“…BRCA1 and BRCA2 are known genetic risk factors for breast and ovarian cancers. These gene mutations are reported in 3% of breast cancer and 10–15% of ovarian cancers [ 1 , 2 ], and are strongly associated with cancer development. A family history of multiple breast or ovarian cancer accounts for about 15% of all breast cancer cases [ 3 ], suggesting that an integrated investigation of breast and ovarian cancers should lead to a better understanding of these cancers.…”

Emerging role of m6A methylation modification in ovarian cancer

“…Referring to immunotherapy, checkpoint inhibitors have poor efficacy because most OCs are characterized by low levels of neoantigens on cancer cells [ 17 ]. In summary, OC is still incurable [ 17 – 19 ]. Therefore, a greater understanding of the signalling cascades involved in OC progression to identify markers for surveillance detection and targets for new therapies will aid in diagnosis and treatment, which are vital to clinical outcomes for OC patients.…”

Epigenetic Mechanism and Survival Prognosis Analysis of Serum Exosomes from Ovarian Cancer Patients based on Sequencing Technology and Bioinformatics

“…Epigenetics is the premise of studying heritable changes in gene expression and function that do not involve DNA sequence alterations through certain mechanisms, mainly including regulatory mechanisms such as DNA methylation, histone modi cation, and RNA editing (Tran, MacFarlane, Kong, O'Connor, & Yu, 2016).As research has progressed, it has been found that epigenetic inheritance plays an important role in the development of a variety of major diseases. In ovarian cancer, endometrial cancer, as well as cervical cancer, there have been many studies demonstrating the in uence of genetic and epigenetic modi cations on tumor initiation and progression(Efthymia Papakonstantinoua et al, 2020;Oliveira et al, 2021;Xie et al, 2021). LncRNAs are a class of RNAs with transcripts longer than 200nt that play important regulatory roles in regulating gene expression, life development and disease development, and mainly in the nucleus to regulate epigenetic modi cations (Hosono et al, 2017).In this study, we aimed to explore the signaling axis of epigenetic modi cation in serum exosomes from ovarian cancer patients and their potential therapeutic targets using whole transcriptome sequencing, TEM, and Sanger analysis.…”