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Cancers
Special Issues
Ovarian Cancer Progression: From Experimental Models to Clinical Applications
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Ovarian Cancer Progression: From Experimental Models to Clinical Applications

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

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 7873

Special Issue Editors

Dr. Marcin Iwanicki

E-Mail Website
Guest Editor
Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA
Interests: ovarian cancer; mesothelial cells; live-cell imaging; metastasis; basement membrane; extracellular matrix
Special Issues, Collections and Topics in MDPI journals
Dr. Mikołaj Piotr Zaborowski

E-Mail Website
Guest Editor
Department of Gynecology Obstetrics and Gynecologic Oncology, Poznan University of Medical Sciences, Poznań, Poland
Interests: ovarian cancer; extracellular vesicles; metastasis; cancer genomics; mathematical modeling; omics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The combination of cytoreductive surgery and chemotherapy for ovarian cancer is initially successful in decreasing tumor volume; however, the management of recurrent and progressive disease remains a significant treatment challenge. Discerning the enormous complexity of disease progression, through efforts that integrate disease biology with high-throughput computation and image-guided approaches, will contribute to the development of new treatment strategies. This Special Issue will be a platform to present interdisciplinary views about ovarian cancer progression. We would like to invite leaders in the field of ovarian cancer cell biology, computational biology, clinical diagnosis, and management. Authors should discuss the latest advances in ovarian cancer models (tissue and mouse models) and computational (omics, artificial intelligence) and imaging approaches. We especially encourage translational studies that identify links between biology and clinical application. We encourage submitting both original research and review articles. The focus areas include, but are not limited to:

A. Cell biology of disease progression.

  • Spheroids, organoids, patient-derived xenografts, and genetically modified mouse models to study the biology of disease progression.
  • Biology of tumor microenvironment: The contribution of mesothelial, mesenchymal, neuronal, fibroblastic, and immune cells to tumor progression.

B. Omics and computational approaches to discover vulnerabilities of progressive disease.

  • Drug screens
  • Genomics/proteomics
  • Immunogenomics
  • Radiomics
  • Artificial intelligence-guided experimental approaches.

C. Clinical diagnosis and management of disease progression.

  • Impact of chemotherapy on metastasis
  • Targeted therapies in relapsed tumors
  • Imaging of recurrent disease
  • Surgical management of recurrent disease
  • Intraoperative imaging
  • Artificial intelligence-based patient stratification.

We strongly encourage studies that combine focus areas and methodologies.

Dr. Marcin Iwanicki
Dr. Mikołaj Piotr Zaborowski
Guest Editors

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 progression
  • ovarian cancer spheroids
  • ovarian cancer organoids
  • ovarian cancer patient-derived xenograft models
  • genetically modified mouse models of ovarian cancer
  • mesothelial cells
  • mesenchymal stem cells
  • cancer-associated fibroblasts
  • ovarian cancer innervation
  • immune models of ovarian cancer
  • omics of ovarian cancer
  • clinical imaging of ovarian cancer
  • metastasis
  • relapse
  • modelling

Published Papers (4 papers)

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Research

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18 pages, 949 KiB  
Article
Characterization of BRCA Deficiency in Ovarian Cancer
by Giovanna Barbero, Roberta Zuntini, Pamela Magini, Laura Desiderio, Michela Bonaguro, Anna Myriam Perrone, Daniela Rubino, Mina Grippa, Antonio De Leo, Claudio Ceccarelli, Lea Godino, Sara Miccoli, Simona Ferrari, Donatella Santini, Pierandrea De Iaco, Claudio Zamagni, Giovanni Innella and Daniela Turchetti
Cancers 2023, 15(5), 1530; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051530 - 28 Feb 2023
Viewed by 1380
Abstract
BRCA testing is recommended in all Ovarian Cancer (OC) patients, but the optimal approach is debated. The landscape of BRCA alterations was explored in 30 consecutive OC patients: 6 (20.0%) carried germline pathogenic variants, 1 (3.3%) a somatic mutation of BRCA2, 2 [...] Read more.
BRCA testing is recommended in all Ovarian Cancer (OC) patients, but the optimal approach is debated. The landscape of BRCA alterations was explored in 30 consecutive OC patients: 6 (20.0%) carried germline pathogenic variants, 1 (3.3%) a somatic mutation of BRCA2, 2 (6.7%) unclassified germline variants in BRCA1, and 5 (16.7%) hypermethylation of the BRCA1 promoter. Overall, 12 patients (40.0%) showed BRCA deficit (BD), due to inactivation of both alleles of either BRCA1 or BRCA2, while 18 (60.0%) had undetected/unclear BRCA deficit (BU). Regarding sequence changes, analysis performed on Formalin-Fixed-Paraffin-Embedded tissue through a validated diagnostic protocol showed 100% accuracy, compared with 96.3% for Snap-Frozen tissue and 77.8% for the pre-diagnostic Formalin-Fixed-Paraffin-Embedded protocol. BD tumors, compared to BU, showed a significantly higher rate of small genomic rearrangements. After a median follow-up of 60.3 months, the mean PFS was 54.9 ± 27.2 months in BD patients and 34.6 ± 26.7 months in BU patients (p = 0.055). The analysis of other cancer genes in BU patients identified a carrier of a pathogenic germline variant in RAD51C. Thus, BRCA sequencing alone may miss tumors potentially responsive to specific treatments (due to BRCA1 promoter methylation or mutations in other genes) while unvalidated FFPE approaches may yield false-positive results. Full article
(This article belongs to the Special Issue Ovarian Cancer Progression: From Experimental Models to Clinical Applications)
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15 pages, 3754 KiB  
Article
Expression Profiles of ID and E2A in Ovarian Cancer and Suppression of Ovarian Cancer by the E2A Isoform E47
by Yong-Jae Lee, Eun-Ji Nam, Sunghoon Kim, Young-Tae Kim, Pamela Itkin-Ansari and Sang-Wun Kim
Cancers 2022, 14(12), 2903; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14122903 - 12 Jun 2022
Cited by 1 | Viewed by 1773
Abstract
The E2A and inhibitor of DNA binding (ID) proteins are transcription factors involved in cell cycle regulation and cellular differentiation. Imbalance of ID/E2A activity is associated with oncogenesis in various tumors, but their expression patterns and prognostic values are still unknown. We evaluated [...] Read more.
The E2A and inhibitor of DNA binding (ID) proteins are transcription factors involved in cell cycle regulation and cellular differentiation. Imbalance of ID/E2A activity is associated with oncogenesis in various tumors, but their expression patterns and prognostic values are still unknown. We evaluated ID and E2A expression in ovarian cancer cells, and assessed the possibility of reprogramming ovarian cellular homeostasis by restoring the ID/E2A axis. We analyzed copy number alterations, mutations, methylations, and mRNA expressions of ID 1–4 and E2A using The Cancer Genome Atlas data of 570 ovarian serous cystadenocarcinoma patients. Incidentally, 97.2% cases exhibited gain of ID 1–4 or loss of E2A. Predominantly, ID 1–4 were hypomethylated, while E2A was hypermethylated. Immunohistochemical analysis revealed that ID-3 and ID-4 expressions were high while E2A expression was low in cancerous ovarian tissues. Correlation analysis of ID and E2A levels with survival outcomes of ovarian cancer patients indicated that patients with high ID-3 levels had poor overall survival. We also determined the effect of E2A induction on ovarian cancer cell growth in vitro and in vivo using SKOV-3/Luc cells transduced with tamoxifen-inducible E47, a splice variant of E2A. Interestingly, E47 induced SKOV-3 cell death in vitro and inhibited tumor growth in SKOV-3 implanted mice. Therefore, restoring ID/E2A balance is a promising approach for treating ovarian cancer. Full article
(This article belongs to the Special Issue Ovarian Cancer Progression: From Experimental Models to Clinical Applications)
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17 pages, 5589 KiB  
Article
Suppression of the ABCA1 Cholesterol Transporter Impairs the Growth and Migration of Epithelial Ovarian Cancer
by Jixuan Gao, MoonSun Jung, Rebekka T. Williams, Danica Hui, Amanda J. Russell, Andrea J. Naim, Alvin Kamili, Molly Clifton, Angelika Bongers, Chelsea Mayoh, Gwo Ho, Clare L. Scott, Wendy Jessup, Michelle Haber, Murray D. Norris, Michelle J. Henderson and on behalf of Australian Ovarian Cancer Study
Cancers 2022, 14(8), 1878; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14081878 - 08 Apr 2022
Cited by 11 | Viewed by 2387
Abstract
Background: Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy with over 80% of cases already disseminated at diagnosis and facing a dismal five-year survival rate of 35%. EOC cells often spread to the greater omentum where they take-up cholesterol. Excessive amounts [...] Read more.
Background: Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy with over 80% of cases already disseminated at diagnosis and facing a dismal five-year survival rate of 35%. EOC cells often spread to the greater omentum where they take-up cholesterol. Excessive amounts of cholesterol can be cytocidal, suggesting that cholesterol efflux through transporters may be important to maintain homeostasis, and this may explain the observation that high expression of the ATP-binding cassette A1 (ABCA1) cholesterol transporter has been associated with poor outcome in EOC patients. Methods: ABCA1 expression was silenced in EOC cells to investigate the effect of inhibiting cholesterol efflux on EOC biology through growth and migration assays, three-dimensional spheroid culture and cholesterol quantification. Results: ABCA1 suppression significantly reduced the growth, motility and colony formation of EOC cell lines as well as the size of EOC spheroids, whilst stimulating expression of ABCA1 reversed these effects. In serous EOC cells, ABCA1 suppression induced accumulation of cholesterol. Lowering cholesterol levels using methyl-B-cyclodextrin rescued the effect of ABCA1 suppression, restoring EOC growth. Furthermore, we identified FDA-approved agents that induced cholesterol accumulation and elicited cytocidal effects in EOC cells. Conclusions: Our data demonstrate the importance of ABCA1 in maintaining cholesterol balance and malignant properties in EOC cells, highlighting its potential as a therapeutic target for this disease. Full article
(This article belongs to the Special Issue Ovarian Cancer Progression: From Experimental Models to Clinical Applications)
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Review

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18 pages, 1145 KiB  
Review
The Role of Circulating Tumor Cells in Ovarian Cancer Dissemination
by Anna Szczerba, Aleksandra Śliwa, Pawel P. Pieta and Anna Jankowska
Cancers 2022, 14(24), 6030; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14246030 - 07 Dec 2022
Cited by 5 | Viewed by 1459
Abstract
Metastatic ovarian cancer is the main reason for treatment failures and consequent deaths. Ovarian cancer is predisposed to intraperitoneal dissemination. In comparison to the transcoelomic route, distant metastasis via lymph vessels and blood is less common. The mechanisms related to these two modes [...] Read more.
Metastatic ovarian cancer is the main reason for treatment failures and consequent deaths. Ovarian cancer is predisposed to intraperitoneal dissemination. In comparison to the transcoelomic route, distant metastasis via lymph vessels and blood is less common. The mechanisms related to these two modes of cancer spread are poorly understood. Nevertheless, the presence of tumor cells circulating in the blood of OC patients is a well-established phenomenon confirming the significant role of lymphatic and hematogenous metastasis. Thus, the detection of CTCs may provide a minimally invasive tool for the identification of ovarian cancer, monitoring disease progression, and treatment effectiveness. This review focuses on the biology of ovarian CTCs and the role they may play in cancer diagnosis and therapy. Full article
(This article belongs to the Special Issue Ovarian Cancer Progression: From Experimental Models to Clinical Applications)
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