Epigenetic Mechanisms and Therapeutic Targets in Chemoresistant High-Grade Serous Ovarian Cancer

Matthews, Bayley G.; Wong‐Brown, Michelle W.

doi:10.3390/cancers13235993

Cited by 23 publications

(20 citation statements)

References 112 publications

(153 reference statements)

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“…DNA methylation mediates the silencing of transcription and aberrant gene promoter methylation. The role of DNA methylation in the progression and chemoresistance in high-grade serous ovarian cancer at both the genome-wide and individual gene level has been recently reviewed [ 75 ].…”

Section: Folate Homeostasis Folate Transport and One-carbon Metabolismmentioning

confidence: 99%

Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

Wallace-Povirk

Hou

Nayeen

et al. 2021

Cancers

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New therapies are urgently needed for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. To identify new approaches for targeting EOC, metabolic vulnerabilities must be discovered and strategies for the selective delivery of therapeutic agents must be established. Folate receptor (FR) α and the proton-coupled folate transporter (PCFT) are expressed in the majority of EOCs. FRβ is expressed on tumor-associated macrophages, a major infiltrating immune population in EOC. One-carbon (C1) metabolism is partitioned between the cytosol and mitochondria and is important for the synthesis of nucleotides, amino acids, glutathione, and other critical metabolites. Novel inhibitors are being developed with the potential for therapeutic targeting of tumors via FRs and the PCFT, as well as for inhibiting C1 metabolism. In this review, we summarize these exciting new developments in targeted therapies for both tumors and the tumor microenvironment in EOC.

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Section: Folate Homeostasis Folate Transport and One-carbon Metabolismmentioning

confidence: 99%

Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

Wallace-Povirk

Hou

Nayeen

et al. 2021

Cancers

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“…The overall survival rate of HGSOC has not been improved in the last three decades, and most patients develop recurrent disease within 3 years and died from the disease within 5 years. HGSOC is extremely regulated by epigenetic modifications ( 27 ). M 6 A plays an important role in numerous biological processes, which contributes to cancer development, cancer cell proliferation and cancer stem cell self-renewal ( 28 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of m6A-modified circRNAs in peritoneal metastasis of high grade serious carcinoma of ovary

Guo

Xu²,

Qiu³

et al. 2022

Front. Oncol.

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PurposeHigh-grade serous ovarian cancer (HGSOC) remains the most lethal female cancer due to metastasis. CircRNAs are recently identified to be modified by N6-methyladenosine (m6A) in many cells. However, the significance of m6A-modified circular RNAs (circRNAs) has not been elucidated in HGSOC peritoneal metastasis. Here, we aimed to investigate the participation and potential functions of m6A-modified circRNAs in HGSCO peritoneal metastasis.MethodsCancerous tissues were collected from the in situ and the peritoneal metastasis lesions of HGSCO patients. M6A-tagged circRNAs were identified by m6A-modified RNA immunoprecipitation sequencing (m6A-RIP-seq). Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of the m6A-modified circRNAs.ResultsFor the m6A-modified circRNAs, 259 were upregulated and 227 were downregulated in the peritoneal metastasis than in the situ lesions of HGSCO patients. For the m6A peaks, 1541 were upregulated and 1293 were downregulated in the peritoneal metastasis than in the in situ lesions of HGSCO patients. For the differential expressed circRNAs, 1911(19.6%) were upregulated and 2883(29.6%) were downregulated in the peritoneal metastasis than in the in situ lesions of HGSCO patients. The upregulated m6A-modified circRNAs were associated with the HIF-1 signaling. The downregulated m6A-modified circRNAs were associated with the MAPK signaling.ConclusionsThis work firstly identified the transcriptome-wide map of m6A-modified circRNAs in peritoneal metastasis of HGSCO. Our findings provided novel evidences about the participation of m6A-modified circRNAs via HIF-1 and MAPK signaling and a new insight in molecular target of HGSCO peritoneal metastasis.

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“…Macintyre et al [53] identified seven copy number signatures that were stable between diagnosis and disease relapse, indicating that copy number signatures at diagnosis may predict overall survival and platinum resistance [54] . Different mutational processes generate unique combinations of mutation types, termed mutational signatures [55] . The Catalogue of Somatic Mutations in Cancer (COSMIC) has revealed many mutational signatures across the spectrum of human cancer types.…”

Section: Geneticsmentioning

confidence: 99%

“…The Catalogue of Somatic Mutations in Cancer (COSMIC) has revealed many mutational signatures across the spectrum of human cancer types. Analysis of COSMIC mutational signatures in ovarian cancer reveals a prevalence of signature 1B [ 56 ] .…”

Section: Future Directionsmentioning

confidence: 99%

Ovarian cancer resistance to PARPi and platinum-containing chemotherapy

Summey¹,

Uyar²

2022

Cancer Drug Resist

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Epithelial ovarian cancer remains the most lethal female malignancy despite options for systemic therapy and the emergence of targeted therapies. Although initial response to therapy is observed, recurrence and ultimately chemoresistance result in overall therapeutic failure. This pattern has been evident with platinum therapy since the 1980s. Significant excitement surrounded the approval of poly (ADP-ribose) polymerase inhibition (PARPi) as a novel therapeutic option, especially with the advent of personalized medicine, but resistance has similarly developed to these treatments. Novel agents are constantly being sought, but if the obstacle of chemoresistance remains, the durability of responses will remain tenuous. Unraveling the multifactorial mechanisms of platinum and PARPi resistance is increasingly important as a therapeutic failure with current strategies is almost assured. Focusing greater efforts on expanding the current understanding of the complex nature of platinum and PARPi chemoresistance has tremendous potential to improve clinical outcomes.

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Epigenetic Mechanisms and Therapeutic Targets in Chemoresistant High-Grade Serous Ovarian Cancer

Cited by 23 publications

References 112 publications

Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

Comprehensive analysis of m6A-modified circRNAs in peritoneal metastasis of high grade serious carcinoma of ovary

Ovarian cancer resistance to PARPi and platinum-containing chemotherapy

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