Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer

Muñoz-Galván, Sandra; Carnero, Amancio

doi:10.3390/cancers13164029

Cited by 12 publications

(7 citation statements)

References 104 publications

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“…These heterocellular aggregate structures are designated “metastatic units” because of their unique contributions to tumor spread within the peritoneal cavity and construction of the metastatic niche [ 86 ]. Indeed, recent transcriptomic, epigenomic, mass spectroscopy, spatial transcriptomic and multiplexed imaging approaches, at both the bulk tumor and single-cell levels, clarified the complexity of the cellular interactions in the ovarian tumor microenvironment underlying development of resistance to chemotherapy (e.g., [ 93 , 94 , 95 ]).…”

Section: Heterotypic Spheroids: a Specialized Caf–tumor Microenvironmentmentioning

confidence: 99%

Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets

Czekay

Cheon

Samarakoon

et al. 2022

Cancers

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Cancer-associated fibroblasts (CAFs) are a heterogenous population of stromal cells found in solid malignancies that coexist with the growing tumor mass and other immune/nonimmune cellular elements. In certain neoplasms (e.g., desmoplastic tumors), CAFs are the prominent mesenchymal cell type in the tumor microenvironment, where their presence and abundance signal a poor prognosis in multiple cancers. CAFs play a major role in the progression of various malignancies by remodeling the supporting stromal matrix into a dense, fibrotic structure while secreting factors that lead to the acquisition of cancer stem-like characteristics and promoting tumor cell survival, reduced sensitivity to chemotherapeutics, aggressive growth and metastasis. Tumors with high stromal fibrotic signatures are more likely to be associated with drug resistance and eventual relapse. Clarifying the molecular basis for such multidirectional crosstalk among the various normal and neoplastic cell types present in the tumor microenvironment may yield novel targets and new opportunities for therapeutic intervention. This review highlights the most recent concepts regarding the complexity of CAF biology including CAF heterogeneity, functionality in drug resistance, contribution to a progressively fibrotic tumor stroma, the involved signaling pathways and the participating genes.

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Section: Heterotypic Spheroids: a Specialized Caf–tumor Microenvironmentmentioning

confidence: 99%

Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets

Czekay

Cheon

Samarakoon

et al. 2022

Cancers

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“…Thus, a combination treatment of pGSN inhibition and ICI could considerably enhance OVCA patient outcomes. Epigenetic alterations, including DNA methylation and histone modifications, cause chemotherapy resistance in ovarian cancer [ 111 ]. DNA methyltransferase 1 and histone deacetylase are involved in epigenetic alteration [ 112 , 113 ].…”

Section: Summary and Future Research Directionsmentioning

confidence: 99%

Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of Chemoresistance

Onuma

Asare-Werehene

Yoshida

et al. 2022

Cells

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Ovarian Cancer (OVCA) is the most fatal gynecologic cancer and has a 5-year survival rate less than 45%. This is mainly due to late diagnosis and drug resistance. Overexpression of plasma gelsolin (pGSN) is key contributing factor to OVCA chemoresistance and immunosuppression. Gelsolin (GSN) is a multifunctional protein that regulates the activity of actin filaments by cleavage, capping, and nucleation. Generally, it plays an important role in cytoskeletal remodeling. GSN has three isoforms: cytosolic GSN, plasma GSN (pGSN), and gelsolin-3. Exosomes containing pGSN are released and contribute to the progression of OVCA. This review describes how pGSN overexpression inhibits chemotherapy-induced apoptosis and triggers positive feedback loops of pGSN expression. It also describes the mechanisms by which exosomal pGSN promotes apoptosis and dysfunction in tumor-killing immune cells. A discussion on the potential of pGSN as a prognostic, diagnostic, and therapeutic marker is also presented herein.

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“…However, existing studies have found that the pathogenesis of OCCC is similar to endometrial cancer, such as inactivation of tumor suppressor genes such as PTEN (phosphatase and tensin homologue) and ARID1A (AT-rich interactive domain 1A), activation of the PI3K/AKT/mTOR (phosphoinositide-3 kinase/protein kinase-B/mammalian) signal pathway, and high microsatellite instability (MSI) ( Ueda et al, 2005 ; Gounaris et al, 2011 ; Xiao et al, 2012 ; Worley et al, 2015 ; Willis et al, 2017 ). With the development of next-generation sequencing, our knowledge about tumorigenesis and the mechanisms of tumor cell proliferation, immune avoidance and antitumor therapy has increased ( Munoz-Galvan and Carnero, 2021 ). In this review, we summarized recent advances in the molecular characteristics of OCCC from the perspective of genomics and epigenomics ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Review the progression of ovarian clear cell carcinoma from the perspective of genomics and epigenomics

Di²,

Zhao³

et al. 2023

Front. Genet.

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Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer with unique molecular characteristics, specific biological and clinical behavior, poor prognosis and high resistance to chemotherapy. Pushed by the development of genome-wide technologies, our knowledge about the molecular features of OCCC has been considerably advanced. Numerous studies are emerging as groundbreaking, and many of them are promising treatment strategies. In this article, we reviewed studies about the genomics and epigenetics of OCCC, including gene mutation, copy number variations, DNA methylation and histone modifications.

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Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer

Cited by 12 publications

References 104 publications

Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets

Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets

Exosomal Plasma Gelsolin Is an Immunosuppressive Mediator in the Ovarian Tumor Microenvironment and a Determinant of Chemoresistance

Review the progression of ovarian clear cell carcinoma from the perspective of genomics and epigenomics

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