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Cancers
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Advances in Translational Ovarian Cancer Research
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Advances in Translational Ovarian Cancer Research

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 5664

Special Issue Editor

Dr. Jan Kuhlmann

E-Mail Website
Guest Editor
Department of Obstertrics and Gynecology, University of Dresden, Dresden, Germany
Interests: translational research of breast and ovarian cancer

Special Issue Information

Dear Colleagues,

Ovarian cancer is the leading cause of death among female malignancies, and despite advances in targeted therapy approaches, such as antiangiogenic therapy with bevacizumab or the administration of PARP inhibitors, patients with advanced ovarian cancer still face a poor overall prognosis. Therefore, innovative approaches for the diagnosis and personalized treatment of ovarian cancer are urgently needed in order to improve the patient outcome, which is why we are pleased to invite you to submit a manuscript on the current translational research on ovarian cancer. Our Special Issue shall cover the latest research on ovarian cancer, welcoming original articles and reviews with clinical translational implication, research areas including (but not limited to) the following: 

  1. Novel concept for predictive and prognostic biomarkers of potential clinical significance; 
  2. Identification of molecular targets, especially for platinum-resistant or PARPi-resistant ovarian cancer; 
  3. Clinical studies with innovative treatment approaches for ovarian cancer. 

We look forward to receiving your contributions.

Dr. Jan Kuhlman
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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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
  • translational research
  • biomarker
  • targeted therapy
  • platinum resistance
  • PARPi resistance

Published Papers (3 papers)

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Research

22 pages, 4326 KiB  
Article
Establishment and Molecular Characterization of an In Vitro Model for PARPi-Resistant Ovarian Cancer
by Daniel Martin Klotz, Franziska Maria Schwarz, Anna Dubrovska, Kati Schuster, Mirko Theis, Alexander Krüger, Oliver Kutz, Theresa Link, Pauline Wimberger, Stephan Drukewitz, Frank Buchholz, Jürgen Thomale and Jan Dominik Kuhlmann
Cancers 2023, 15(15), 3774; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15153774 - 25 Jul 2023
Cited by 1 | Viewed by 1461
Abstract
Overcoming PARPi resistance is a high clinical priority. We established and characterized comparative in vitro models of acquired PARPi resistance, derived from either a BRCA1-proficient or BRCA1-deficient isogenic background by long-term exposure to olaparib. While parental cell lines already exhibited a [...] Read more.
Overcoming PARPi resistance is a high clinical priority. We established and characterized comparative in vitro models of acquired PARPi resistance, derived from either a BRCA1-proficient or BRCA1-deficient isogenic background by long-term exposure to olaparib. While parental cell lines already exhibited a certain level of intrinsic activity of multidrug resistance (MDR) proteins, resulting PARPi-resistant cells from both models further converted toward MDR. In both models, the PARPi-resistant phenotype was shaped by (i) cross-resistance to other PARPis (ii) impaired susceptibility toward the formation of DNA-platinum adducts upon exposure to cisplatin, which could be reverted by the drug efflux inhibitors verapamil or diphenhydramine, and (iii) reduced PARP-trapping activity. However, the signature and activity of ABC-transporter expression and the cross-resistance spectra to other chemotherapeutic drugs considerably diverged between the BRCA1-proficient vs. BRCA1-deficient models. Using dual-fluorescence co-culture experiments, we observed that PARPi-resistant cells had a competitive disadvantage over PARPi-sensitive cells in a drug-free medium. However, they rapidly gained clonal dominance under olaparib selection pressure, which could be mitigated by the MRP1 inhibitor MK-751. Conclusively, we present a well-characterized in vitro model, which could be instrumental in dissecting mechanisms of PARPi resistance from HR-proficient vs. HR-deficient background and in studying clonal dynamics of PARPi-resistant cells in response to experimental drugs, such as novel olaparib-sensitizers. Full article
(This article belongs to the Special Issue Advances in Translational Ovarian Cancer Research)
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17 pages, 2003 KiB  
Article
Nectin-4 as Blood-Based Biomarker Enables Detection of Early Ovarian Cancer Stages
by Christoph Rogmans, Julia Feuerborn, Leonie Treeck, Nils Tribian, Inken Flörkemeier, Norbert Arnold, Jörg Paul Weimer, Nicolai Maass, Peer Jansen, Wolfgang Lieb, Astrid Dempfle, Dirk O. Bauerschlag and Nina Hedemann
Cancers 2022, 14(23), 5867; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14235867 - 29 Nov 2022
Cited by 4 | Viewed by 1834
Abstract
Ovarian cancer is the third most common gynecological malignancy and has the highest mortality rate. Owing to unspecific symptoms, ovarian cancer is not detected until an advanced stage in about two-thirds of cases. Therefore, it is crucial to establish reliable biomarkers for the [...] Read more.
Ovarian cancer is the third most common gynecological malignancy and has the highest mortality rate. Owing to unspecific symptoms, ovarian cancer is not detected until an advanced stage in about two-thirds of cases. Therefore, it is crucial to establish reliable biomarkers for the early stages to improve the patients’ prognosis. The aim of this study is to investigate whether the ADAM17 substrates Nectin-4, Heparin-binding EGF-like growth factor (HB-EGF) and Amphiregulin (AREG) could function as potential tumor markers for ovarian cancer. In this study a set of 231 sera consisting of 131 ovarian cancer patients and 100 healthy age-matched controls were assembled. Nectin-4, HB-EGF and AREG levels of preoperatively collected sera were determined by enzyme-linked immunosorbent assay (ELISA). Our analysis revealed that Nectin-4 and HB-EGF were significantly increased compared to the age-matched control group (p < 0.0001, p = 0.016). Strikingly, significantly higher Nectin-4 and HB-EGF levels were detected in early-stage FIGO I/II (p <0.001; p = 0.025) compared to healthy controls. Eighty-four percent (16/19) of patients with low Ca-125 levels showed increased Nectin-4 levels. Our study proposes Nectin-4 and HB-EGF as promising blood-based biomarkers for the detection of early stages of ovarian cancer patients that would not have been detected by Ca-125. Full article
(This article belongs to the Special Issue Advances in Translational Ovarian Cancer Research)
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14 pages, 2185 KiB  
Article
Molecular Profiles of Serum-Derived Extracellular Vesicles in High-Grade Serous Ovarian Cancer
by Li Zhao, Sara Corvigno, Shaolin Ma, Joseph Celestino, Nicole D. Fleming, Richard A. Hajek, Adrian Lankenau Ahumada, Nicholas B. Jennings, Erika J. Thompson, Hongli Tang, Shannon N. Westin, Amir A. Jazaeri, Jianhua Zhang, P. Andrew Futreal, Anil K. Sood and Sanghoon Lee
Cancers 2022, 14(15), 3589; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14153589 - 23 Jul 2022
Cited by 1 | Viewed by 1821
Abstract
Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have a response enabling interval cytoreductive surgery. Clinically useful biomarkers for predicting [...] Read more.
Patients with high-grade serous ovarian cancer (HGSC) who have no visible residual disease (R0) after primary surgery have the best clinical outcomes, followed by patients who undergo neoadjuvant chemotherapy (NACT) and have a response enabling interval cytoreductive surgery. Clinically useful biomarkers for predicting these outcomes are still lacking. Extracellular vesicles (EVs) have been recognized as liquid biopsy-based biomarkers for early cancer detection and disease surveillance in other disease settings. In this study, we performed extensive molecular characterization of serum-derived EVs and correlated the findings with therapeutic outcomes in patients with HGSC. Using EV-DNA whole-genome sequencing and EV-RNA sequencing, we identified distinct somatic EV-DNA alterations in cancer-hallmark genes and in ovarian cancer genes, as well as significantly altered oncogenic pathways between the R0 group and NACT groups. We also found significantly altered EV-RNA transcriptomic variations and enriched pathways between the groups. Taken together, our data suggest that the molecular characteristics of EVs could enable prediction of patients with HGSC who could undergo R0 surgery or respond to chemotherapy. Full article
(This article belongs to the Special Issue Advances in Translational Ovarian Cancer Research)
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