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Ovarian Cancer: Recent Advances in Research and Clinical Therapy
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Ovarian Cancer: Recent Advances in Research and Clinical Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 19319

Special Issue Editor

Dr. Mandi Murph

E-Mail Website
Guest Editor
Department of Pharmaceutical and Biomedical Sciences, The University of Georgia College of Pharmacy, Athens, GA 30602, USA
Interests: microRNA; cellular signaling; lysophosphatidic acid

Special Issue Information

Epithelial ovarian carcinoma remains a lethal gynecological malignancy among women across the globe. Although this malignancy is very responsive to therapy, the late-stage disease lacks definitive curability. Modern clinical treatment methods have increased survival rates, but drug resistance and refractory disease in recurrent patients continue to challenge oncologists. Translational research and clinical trials provide hope for the future. In addition, new areas of science may provide revolutionary insights into the drivers of inherited disease and adaptation to drug resistance. Whether immunotherapy will play a prominent role in treatment is still under investigation, as well as the origin of cancer stem cells. This issue will highlight some of the clinical and research advances that sustain hope.

Dr. Mandi Murph
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

  • Epithelial ovarian
  • fallopian tube or primary peritoneal Cancer
  • COVID-19’s impact on treatment
  • Genetic risk correlation – germline or BRCA1/2 somatic mutation testing
  • Platinum-based chemotherapy and DNA repair mechanisms
  • PARP inhibitors and the DNA damage response
  • High- versus low-grade serous carcinoma
  • Circulating biomarkers in recurrence detection
  • Emerging topics: stem cells, immunotherapy, and non-coding RNAs

Published Papers (6 papers)

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Research

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21 pages, 6419 KiB  
Article
Estrogen Receptor-Beta2 (ERβ2)–Mutant p53–FOXM1 Axis: A Novel Driver of Proliferation, Chemoresistance, and Disease Progression in High Grade Serous Ovarian Cancer (HGSOC)
by Chetan C. Oturkar, Nishant Gandhi, Pramod Rao, Kevin H. Eng, Austin Miller, Prashant K. Singh, Emese Zsiros, Kunle O. Odunsi and Gokul M. Das
Cancers 2022, 14(5), 1120; https://doi.org/10.3390/cancers14051120 - 22 Feb 2022
Cited by 14 | Viewed by 2584
Abstract
High grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of epithelial ovarian cancer. Prevalence (~96%) of mutant p53 is a hallmark of HGSOC. Estrogen receptor-beta (ERβ) has been reported to be another important player in HGSOC, although the pro-versus [...] Read more.
High grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of epithelial ovarian cancer. Prevalence (~96%) of mutant p53 is a hallmark of HGSOC. Estrogen receptor-beta (ERβ) has been reported to be another important player in HGSOC, although the pro-versus anti-tumorigenic role of its different isoforms remains unsettled. However, whether there is functional interaction between ERβ and mutant p53 in HGSOC is unknown. ERβ1 and ERβ2 mRNA and protein analysis in HGSOC cell lines demonstrated that ERβ2 is the predominant isoform in HGSOC. Specificity of ERβ2 antibody was ascertained using cells depleted of ERβ2 and ERβ1 separately with isoform-specific siRNAs. ERβ2-mutant p53 interaction in cell lines was confirmed by co-immunoprecipitation and in situ proximity ligation assay (PLA). Expression levels of ERβ2, ERα, p53, and FOXM1 proteins and ERβ2-mutant p53 interaction in patient tumors were determined by immunohistochemistry (IHC) and PLA, respectively. ERβ2 levels correlate positively with FOXM1 levels and negatively with progression-free survival (PFS) and overall survival (OS). Quantitative chromatin immunoprecipitation (qChIP) and mRNA expression analysis revealed that ERβ2 and mutant p53 co-dependently regulated FOXM1 gene transcription. The combination of ERβ2-specific siRNA and PRIMA-1MET that converts mutant p53 to wild type conformation increased apoptosis. Our work provides the first evidence for a novel ERβ2-mutant p53-FOXM1 axis that can be exploited for new therapeutic strategies against HGSOC. Full article
(This article belongs to the Special Issue Ovarian Cancer: Recent Advances in Research and Clinical Therapy)
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11 pages, 2021 KiB  
Article
A Modified Intraperitoneal Chemotherapy Regimen for Ovarian Cancer: Technique and Treatment Outcomes
by Ji Hyun Kim, Hyeong In Ha, Min Hae Kim, Mi Ra Han, Sang-Yoon Park and Myong Cheol Lim
Cancers 2021, 13(19), 4886; https://doi.org/10.3390/cancers13194886 - 29 Sep 2021
Cited by 1 | Viewed by 2639
Abstract
This study aimed to investigate treatment outcomes concerning three institutional modifications to intraperitoneal (IP) chemotherapy for patients with ovarian cancer. The medical records of 27 patients treated with IP chemotherapy were retrospectively reviewed. All patients had three IP chemotherapy institutional modifications; modified Gynecologic [...] Read more.
This study aimed to investigate treatment outcomes concerning three institutional modifications to intraperitoneal (IP) chemotherapy for patients with ovarian cancer. The medical records of 27 patients treated with IP chemotherapy were retrospectively reviewed. All patients had three IP chemotherapy institutional modifications; modified Gynecologic Oncology Group 172 regimen was used for the chemotherapy regimen. With institutional modifications, 63.0% (17/27) completed all six cycles of IP chemotherapy. Of the 17 and 10 patients with primary and recurrent ovarian cancer, respectively, 55.6% (15/27) underwent left colonic surgery, including low anterior resection. In patients with primary ovarian cancer, the IP chemotherapy completion rate was 76.5% (13/17). In patients with and without left colonic surgery, the IP chemotherapy completion rates were 53.3% (8/15) and 75.0% (9/12), respectively. No complications related to left colonic surgery during IP chemotherapy were identified. The most frequent grade 3–4 toxicities were gastrointestinal toxicities (33.3%) and neutropenia (29.6%). The median progression-free survival was 19.5 months in all patients and 25.2 months in patients with primary ovarian cancer. Three institutional modifications to IP chemotherapy increased the completion rate for planned IP chemotherapy, even after left colonic surgery. Further studies involving a larger study cohort are required to confirm survival outcomes using these modifications. Full article
(This article belongs to the Special Issue Ovarian Cancer: Recent Advances in Research and Clinical Therapy)
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20 pages, 3316 KiB  
Article
ADAM17 Inhibition Increases the Impact of Cisplatin Treatment in Ovarian Cancer Spheroids
by Nina Hedemann, Andreas Herz, Jan Hendrik Schiepanski, Jan Dittrich, Susanne Sebens, Astrid Dempfle, Julia Feuerborn, Christoph Rogmans, Nils Tribian, Inken Flörkemeier, Jörg Weimer, Sandra Krüger, Nicolai Maass and Dirk O. Bauerschlag
Cancers 2021, 13(9), 2039; https://doi.org/10.3390/cancers13092039 - 23 Apr 2021
Cited by 16 | Viewed by 4499
Abstract
Chemotherapy resistance is a major challenge in ovarian cancer (OvCa). Thus, novel treatment combinations are highly warranted. However, many promising drug candidates tested in two-dimensional (2D) cell culture have not proved successful in the clinic. For this reason, we analyzed our drug combination [...] Read more.
Chemotherapy resistance is a major challenge in ovarian cancer (OvCa). Thus, novel treatment combinations are highly warranted. However, many promising drug candidates tested in two-dimensional (2D) cell culture have not proved successful in the clinic. For this reason, we analyzed our drug combination not only in monolayers but also in three-dimensional (3D) tumor spheroids. One potential therapeutic target for OvCa is A disintegrin and metalloprotease 17 (ADAM17). ADAM17 can be activated by chemotherapeutics, which leads to enhanced tumor growth due to concomitant substrate cleavage. Therefore, blocking ADAM17 during chemotherapy may overcome resistance. Here, we tested the effect of the ADAM17 inhibitor GW280264X in combination with cisplatin on ovarian cancer cells in 2D and 3D. In 2D, the effect on five cell lines was analyzed with two readouts. Three of these cell lines formed dense aggregates or spheroids (HEY, SKOV-3, and OVCAR-8) in 3D and the treatment effect was analyzed with a multicontent readout (cytotoxicity, viability, and caspase3/7 activation). We tested the combined therapy on tumor spheroids derived from primary patient cells. In 2D, we found a significant reduction in the half minimal (50%) inhibitory concentration (IC50) value of the combined treatment (GW280264X plus cisplatin) in comparison with cisplatin monotherapy in all five cell lines with both 2D readout assays (viability and caspase activation). In contrast, the combined treatment only showed an IC50 reduction in HEY and OVCAR-8 3D tumor spheroid models using caspase3/7 activity or CelltoxTM Green as the readout. Finally, we found an improved effect of GW280264X with cisplatin in tumor spheroids derived from patient samples. In summary, we demonstrate that ADAM17 inhibition is a promising treatment strategy in ovarian cancer. Full article
(This article belongs to the Special Issue Ovarian Cancer: Recent Advances in Research and Clinical Therapy)
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13 pages, 1287 KiB  
Article
Tumor Growth Rate Estimates Are Independently Predictive of Therapy Response and Survival in Recurrent High-Grade Serous Ovarian Cancer Patients
by Thomas Bartl, Jasmine Karacs, Caroline Kreuzinger, Stephanie Pfaffinger, Jonatan Kendler, Cristina Ciocsirescu, Andrea Wolf, Alexander Reinthaller, Elias Meyer, Maximilian Brandstetter, Magdalena Postl, Eva Langthaler, Elena Braicu, Ignace Vergote, Paula Cunnea, Charlie Gourley, Wolfgang D. Schmitt, Dan Cacsire Castillo-Tong and Christoph Grimm
Cancers 2021, 13(5), 1076; https://doi.org/10.3390/cancers13051076 - 3 Mar 2021
Cited by 6 | Viewed by 2402
Abstract
This study aimed to assess the predictive value of tumor growth rate estimates based on serial cancer antigen-125 (CA-125) levels on therapy response and survival of patients with recurrent high-grade serous ovarian cancer (HGSOC). In total, 301 consecutive patients with advanced HGSOC (exploratory [...] Read more.
This study aimed to assess the predictive value of tumor growth rate estimates based on serial cancer antigen-125 (CA-125) levels on therapy response and survival of patients with recurrent high-grade serous ovarian cancer (HGSOC). In total, 301 consecutive patients with advanced HGSOC (exploratory cohort: n = 155, treated at the Medical University of Vienna; external validation cohort: n = 146, from the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) consortium) were enrolled. Tumor growth estimates were obtained using a validated two-phase equation model involving serial CA-125 levels, and their predictive value with respect to treatment response to the next chemotherapy and the prognostic value with respect to disease-specific survival and overall survival were assessed. Tumor growth estimates were an independent predictor for response to second-line chemotherapy and an independent prognostic factor for second-line chemotherapy use in both univariate and multivariable analyses, outperforming both the predictive (second line: p = 0.003, HR 5.19 [1.73–15.58] vs. p = 0.453, HR 1.95 [0.34–11.17]) and prognostic values (second line: p = 0.042, HR 1.53 [1.02–2.31] vs. p = 0.331, HR 1.39 [0.71–2.27]) of a therapy-free interval (TFI) < 6 months. Tumor growth estimates were a predictive factor for response to third- and fourth-line chemotherapy and a prognostic factor for third- and fourth-line chemotherapy use in the univariate analysis. The CA-125-derived tumor growth rate estimate may be a quantifiable and easily assessable surrogate to TFI in treatment decision making for patients with recurrent HGSOC. Full article
(This article belongs to the Special Issue Ovarian Cancer: Recent Advances in Research and Clinical Therapy)
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11 pages, 1731 KiB  
Article
Safety and Efficacy of Weekly Paclitaxel and Cisplatin Chemotherapy for Ovarian Cancer Patients with Hypersensitivity to Carboplatin
by Shinichi Tate, Kyoko Nishikimi, Ayumu Matsuoka, Satoyo Otsuka and Makio Shozu
Cancers 2021, 13(4), 640; https://doi.org/10.3390/cancers13040640 - 5 Feb 2021
Cited by 3 | Viewed by 1958
Abstract
Background: This study aimed to evaluate the safety and efficacy of weekly paclitaxel and cisplatin chemotherapy (wTP) in patients with ovarian cancer who developed carboplatin hypersensitivity reaction (HSR). Methods: We retrospectively investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed [...] Read more.
Background: This study aimed to evaluate the safety and efficacy of weekly paclitaxel and cisplatin chemotherapy (wTP) in patients with ovarian cancer who developed carboplatin hypersensitivity reaction (HSR). Methods: We retrospectively investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed carboplatin HSR during previous chemotherapy (carboplatin and paclitaxel) at our institution between 2011 and 2019. After premedication was administered, paclitaxel was administered over 1 h, followed by cisplatin over 1 h (paclitaxel 80 mg/m2; cisplatin 25 mg/m2; 1, 8, 15 day/4 weeks). We investigated the incidence of patients who successfully received wTP for at least one cycle, treatments compliance, progression-free survival (PFS), and overall survival (OS). Results: The median number of wTP administration cycles was 4 (Interquartile Range IQR, 3–7), 71 patients (83%) successfully received wTP, and 15 patients (17%) developed cisplatin HSR. The efficacy of treatment was as follows: 55 (64%) patients completed the scheduled wTP, 9 (10%) patients discontinued due to HSR to cisplatin within 6 cycles, 1 (1%) patient discontinued due to renal toxicity (grade 2) at the 6th cycle, and 21 (24%) patients discontinued due to progressive disease within 6 cycles. The median PFS and OS after administration of wTP were 10.9 months (95% CI: 7.7–17.7) and 25.9 months (95% CI: 19.0–50.2), respectively. Conclusions: wTP was safe and well-tolerated in patients who developed carboplatin HSR. Full article
(This article belongs to the Special Issue Ovarian Cancer: Recent Advances in Research and Clinical Therapy)
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Review

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25 pages, 1708 KiB  
Review
Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment
by Concetta Altamura, Maria Raffaella Greco, Maria Rosaria Carratù, Rosa Angela Cardone and Jean-François Desaphy
Cancers 2021, 13(4), 668; https://doi.org/10.3390/cancers13040668 - 7 Feb 2021
Cited by 18 | Viewed by 3957
Abstract
Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we [...] Read more.
Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment. Full article
(This article belongs to the Special Issue Ovarian Cancer: Recent Advances in Research and Clinical Therapy)
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