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Ovarian Cancer: From Molecular Mechanisms to Targeted Therapy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 January 2024) | Viewed by 6440

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Special Issue Editor

Prof. Dr. Kentaro Nakayama

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Guest Editor

Department of Obstetrics and Gynecology, School of Medicine, Shimane University, Shimane 693-8501, Japan
Interests: ovarian cancer; precision oncology; panel sequencing; targeted therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ovarian cancer is the most lethal gynecological disease with various histological types, including high-grade serous, mucinous, endometrioid, clear-cell, and low-grade serous carcinomas. Due to the lack of symptoms associated with tumor development and the absence of a reliable screening regimen, most patients are diagnosed at later times, making the disease hard to treat. Recent studies have identified that each histotype of ovarian cancer shows different molecular mechanisms of carcinogenesis. Although carcinogenesis and molecular profiling are distinct among histological types, the treatment regimen is not histology-specific (i.e., Platinum–taxane is still a standard first-line regimen). In light of this, there will be a Special Issue in the International Journal of Molecular Sciences, “Ovarian Cancer: From Molecular Mechanisms to Targeted Therapy”, which will focus on how genomics, epigenomics, and proteomics are altered in ovarian cancer progression and the field of molecular-targeted therapy in ovarian cancer.

We invite you to contribute original articles on carcinogenesis; tumor microenvironment; in vitro/vivo models; organoid models; and targeted therapies that utilize clinical samples, cancer stem cells, next-generation sequencing, circular RNA, and exosomes in as many models and contexts as possible. In addition, recently increased longevity has caused the aging of not only ovarian but many other cancer patients. Along with the invention of new chemo drugs, patients’ tolerability should be taken into consideration, particularly that of older patients. Malnutrition and sarcopenia are frequently observed among seniors and have been recognized as modifiable prognostic factors. It has been recognized that nutritional care and rehabilitation can be effective supportive therapy for cancer patients. Review articles describing recent topics, including precision oncology using panel sequencing, tumor heterogeneity, cancer metabolism, immunotherapy, and attractive supportive therapy in ovarian cancer, are also welcome.

Prof. Dr. Kentaro Nakayama
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

ovarian cancer
cancer organoid
exosomes
clinical sequencing
cancer metabolism
immunotherapy
personalized medicine
molecular target therapy

Published Papers (5 papers)

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Research

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28 pages, 5967 KiB

Open AccessArticle

A Multi-Faceted Analysis Showing CRNDE Transcripts and a Recently Confirmed Micropeptide as Important Players in Ovarian Carcinogenesis

by Anna Balcerak, Laura Aleksandra Szafron, Tymon Rubel, Bianka Swiderska, Arkadiusz M. Bonna, Magdalena Konarzewska, Ireneusz Sołtyszewski, Jolanta Kupryjanczyk and Lukasz Michal Szafron

Int. J. Mol. Sci. 2024, 25(8), 4381; https://doi.org/10.3390/ijms25084381 - 16 Apr 2024

Viewed by 480

Abstract

CRNDE is considered an oncogene expressed as long non-coding RNA. Our previous paper is the only one reporting CRNDE as a micropeptide-coding gene. The amino acid sequence of this micropeptide (CRNDEP) has recently been confirmed by other researchers. This study aimed at providing a mass spectrometry (MS)-based validation of the CRNDEP sequence and an investigation of how the differential expression of CRNDE(P) influences the metabolism and chemoresistance of ovarian cancer (OvCa) cells. We also assessed cellular localization changes of CRNDEP, looked for its protein partners, and bioinformatically evaluated its RNA-binding capacities. Herein, we detected most of the CRNDEP sequence by MS. Moreover, our results corroborated the oncogenic role of CRNDE, portraying it as the gene impacting carcinogenesis at the stages of DNA transcription and replication, affecting the RNA metabolism, and stimulating the cell cycle progression and proliferation, with CRNDEP being detected in the centrosomes of dividing cells. We also showed that CRNDEP is located in nucleoli and revealed interactions of this micropeptide with p54, an RNA helicase. Additionally, we proved that high CRNDE(P) expression increases the resistance of OvCa cells to treatment with microtubule-targeted cytostatics. Furthermore, altered CRNDE(P) expression affected the activity of the microtubular cytoskeleton and the formation of focal adhesion plaques. Finally, according to our in silico analyses, CRNDEP is likely capable of RNA binding. All these results contribute to a better understanding of the CRNDE(P) role in OvCa biology, which may potentially improve the screening, diagnosis, and treatment of this disease. Full article

(This article belongs to the Special Issue Ovarian Cancer: From Molecular Mechanisms to Targeted Therapy)

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21 pages, 48324 KiB

Open AccessArticle

Identification of TRPM2 as a Potential Therapeutic Target Associated with Immune Infiltration: A Comprehensive Pan-Cancer Analysis and Experimental Verification in Ovarian Cancer

by Danxi Zheng, Siyu Long and Mingrong Xi

Int. J. Mol. Sci. 2023, 24(15), 11912; https://doi.org/10.3390/ijms241511912 - 25 Jul 2023

Cited by 1 | Viewed by 1313

Abstract

The exact role of Transient receptor potential melastatin 2 (TRPM2) in tumor progression and immunomodulation remains elusive. We comprehensively investigated the expression pattern, diagnostic value, prognostic impact, genetic and epigenetic alterations of TRPM2 in pan-cancer. Then, we explored underlying pathways associated with TRPM2 and immune-related signatures. Ovarian cancer (OV) specimens were enrolled to test the expression of TRPM2 by immunohistochemistry and RT-qPCR. OV cell A2780 transfected with shRNA targeting TRPM2 was used in subsequent experiments. TRPM2 was aberrantly expressed and associated with unfavorable prognosis across various cancers. It possesses significant diagnostic values with AUC > 0.90. TRPM2 participated in pathways mediating immunoregulation and tumorigenesis. The expression of TRPM2 was significantly correlated with tumor microenvironment scores, tumor-stemness index, macrophages infiltration, immune checkpoints, and immune-related genes. OV single-cell datasets also indicated that TRPM2 was predominantly distributed on macrophages and malignancies. The overexpressed TRPM2 in OV tissues was validated at both the mRNA and protein levels. TRPM2 expression was significantly correlated with type2 macrophage marker CD206. Knockdown of TRPM2 inhibited OV cell proliferation and promoted apoptosis. Overall, TRPM2 has relevance to an immunosuppressive tumor microenvironment by modulating macrophage. It could serve as a powerful biomarker for tumor screening and prognosis, and a potential therapeutic target for tumor treatment, especially for OV. Full article

(This article belongs to the Special Issue Ovarian Cancer: From Molecular Mechanisms to Targeted Therapy)

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14 pages, 3952 KiB

Open AccessArticle

Mechanism of Cell Death by Combined Treatment with an xCT Inhibitor and Paclitaxel: An Alternative Therapeutic Strategy for Patients with Ovarian Clear Cell Carcinoma

by Urara Idei, Tsuyoshi Ohta, Hizuru Yamatani, Manabu Seino and Satoru Nagase

Int. J. Mol. Sci. 2023, 24(14), 11781; https://doi.org/10.3390/ijms241411781 - 22 Jul 2023

Cited by 3 | Viewed by 1146

Abstract

Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian carcinoma that responds poorly to chemotherapy. Glutathione (GSH) is a primary antioxidant, which protects cells against reactive oxygen species (ROS). High levels of GSH are related to chemotherapeutic resistance. The glutamine/cystine transporter xCT is essential for intracellular GSH synthesis. However, whether xCT inhibition can overcome the resistance to chemotherapeutic agents in OCCC remains unclear. This study demonstrated that combined treatment with paclitaxel (PTX) and the xCT inhibitor sulfasalazine (SAS) significantly enhanced cytotoxicity more than the individual drugs did in OCCC cells. Treatment with PTX and SAS induced apoptosis more effectively than did individual drug treatments in the cells with significant generation of ROS. Moreover, combined treatment with PTX and SAS induced ferroptosis in the cells with low expression of glutathione peroxidase (GPx4), high levels of intracellular iron and significant lipid ROS accumulation. Therefore, our findings provide valuable information that the xCT inhibitor might be a promising therapeutic target for drug-resistant OCCC. The strategy of combined administration of PTX and SAS can potentially be used to treat OCCC and help to develop novel therapeutic methods. Full article

(This article belongs to the Special Issue Ovarian Cancer: From Molecular Mechanisms to Targeted Therapy)

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Review

Jump to: Research

25 pages, 2330 KiB

Open AccessReview

Developments in Genetics: Better Management of Ovarian Cancer Patients

by Ovidiu-Virgil Maioru, Viorica-Elena Radoi, Madalin-Codrut Coman, Iulian-Andrei Hotinceanu, Andra Dan, Anca-Elena Eftenoiu, Livia-Mălina Burtavel, Laurentiu-Camil Bohiltea and Emilia-Maria Severin

Int. J. Mol. Sci. 2023, 24(21), 15987; https://doi.org/10.3390/ijms242115987 - 05 Nov 2023

Cited by 1 | Viewed by 2024

Abstract

The purpose of this article is to highlight the new advancements in molecular and diagnostic genetic testing and to properly classify all ovarian cancers. In this article, we address statistics, histopathological classification, molecular pathways implicated in ovarian cancer, genetic screening panels, details about [...] Read more.

(This article belongs to the Special Issue Ovarian Cancer: From Molecular Mechanisms to Targeted Therapy)

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19 pages, 542 KiB

Open AccessReview

The Contribution of Lipidomics in Ovarian Cancer Management: A Systematic Review

by Vasiliki Tzelepi, Helen Gika, Olga Begou and Eleni Timotheadou

Int. J. Mol. Sci. 2023, 24(18), 13961; https://doi.org/10.3390/ijms241813961 - 11 Sep 2023

Viewed by 881

Abstract

Lipidomics is a comprehensive study of all lipid components in living cells, serum, plasma, or tissues, with the aim of discovering diagnostic, prognostic, and predictive biomarkers for diseases such as malignant tumors. This systematic review evaluates studies, applying lipidomics to the diagnosis, prognosis, prediction, and differentiation of malignant and benign ovarian tumors. A literature search was performed in PubMed, Science Direct, and SciFinder. Only publications written in English after 2012 were included. Relevant citations were identified from the reference lists of primary included studies and were also included in our list. All studies included referred to the application of lipidomics in serum/plasma samples from human cases of OC, some of which also included tumor tissue samples. In some of the included studies, metabolome analysis was also performed, in which other metabolites were identified in addition to lipids. Qualitative data were assessed, and the risk of bias was determined using the ROBINS-I tool. A total of twenty-nine studies were included, fifteen of which applied non-targeted lipidomics, seven applied targeted lipidomics, and seven were reviews relevant to our objectives. Most studies focused on the potential application of lipidomics in the diagnosis of OC and showed that phospholipids and sphingolipids change most significantly during disease development. In conclusion, this systematic review highlights the potential contribution of lipids as biomarkers in OC management. Full article

(This article belongs to the Special Issue Ovarian Cancer: From Molecular Mechanisms to Targeted Therapy)

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