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Cancers
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Advances in the Treatment of Ovarian Cancer
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Advances in the Treatment of Ovarian Cancer

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

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 8743

Special Issue Editor

Dr. Debra L. Richardson

E-Mail Website
Guest Editor
Section of Gynecologic Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Interests: developmental therapeutics; ovarian cancer; endometrial cancer; cervical cancer; phase I clinical trials

Special Issue Information

Dear Colleagues,

Ovarian cancer remains the deadliest gynecologic cancer in the United States, with more than 12,000 estimated deaths expected in 2022. The cure rate has not changed in over 50 years, and the majority of ovarian cancer patients are diagnosed at an advanced stage, with a median overall survival of <5 years. While incidence is gradually declining, prevalence is increasing, in part due to advances in treatment and maintenance strategies, including PARP inhibitors and antiangiogenic agents. Biomarkers, including BRCA and homologous recombination deficiency, play an important role in choosing maintenance therapy and will likely help to guide therapies with the development of antibody drug conjugates. Platinum-resistant ovarian cancer remains an area of high unmet need, where novel strategies are needed to improve outcomes. Low-grade serous ovarian cancer is relatively chemoresistant, so targeted therapies are being developed.

In this Special Issue, we wish to collect original research and review articles addressing all innovations dedicated to ovarian cancer treatment, including PARP inhibitors, antibody drug conjugates, immunotherapy, HIPEC, rate tumor type treatment (e.g., low grade serous, clear cell, mucinous), screening, role of secondary debulking, maintenance strategies post PARPi, and novel therapeutic combinations.

Dr. Debra L. Richardson
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 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

  • PARP inhibitors
  • antibody drug conjugates
  • HIPEC
  • immunotherapy
  • screening
  • secondary debulking
  • ovarian cancer

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Published Papers (3 papers)

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Research

19 pages, 7384 KiB  
Article
Cyclooxygenase-2 Blockade Is Crucial to Restore Natural Killer Cell Activity before Anti-CTLA-4 Therapy against High-Grade Serous Ovarian Cancer
by Fernán Gómez-Valenzuela, Ignacio Wichmann, Felipe Suárez, Sumie Kato, Enrique Ossandón, Marcela Hermoso, Elmer A. Fernández and Mauricio A. Cuello
Cancers 2024, 16(1), 80; https://doi.org/10.3390/cancers16010080 - 22 Dec 2023
Cited by 1 | Viewed by 1459
Abstract
Chronic inflammation influences the tumor immune microenvironment (TIME) in high-grade serous ovarian cancer (HGSOC). Specifically, cyclooxygenase-2 (COX-2) overexpression promotes cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) expression. Notably, elevated COX-2 levels in the TIME have been associated with reduced response to anti-CTLA-4 immunotherapy. However, the precise [...] Read more.
Chronic inflammation influences the tumor immune microenvironment (TIME) in high-grade serous ovarian cancer (HGSOC). Specifically, cyclooxygenase-2 (COX-2) overexpression promotes cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) expression. Notably, elevated COX-2 levels in the TIME have been associated with reduced response to anti-CTLA-4 immunotherapy. However, the precise impact of COX-2, encoded by PTGS2, on the immune profile remains unknown. To address this, we performed an integrated bioinformatics analysis using data from the HGSOC cohorts (TCGA-OV, n = 368; Australian cohort AOCS, n = 80; GSE26193, n = 62; and GSE30161, n = 45). Employing Gene Set Variation Analysis (GSVA), MIXTURE and Ecotyper cell deconvolution algorithms, we concluded that COX-2 was linked to immune cell ecosystems associated with shorter survival, cell dysfunction and lower NK cell effector cytotoxicity capacity. Next, we validated these results by characterizing circulating NK cells from HGSOC patients through flow cytometry and cytotoxic assays while undergoing COX-2 and CTLA-4 blockade. The blockade of COX-2 improved the cytotoxic capacity of NK cells against HGSOC cell lines. Our findings underscore the relevance of COX-2 in shaping the TIME and suggest its potential as a prognostic indicator and therapeutic target. Increased COX-2 expression may hamper the effectivity of immunotherapies that require NK cell effector function. These results provide a foundation for experimental validation and clinical trials investigating combined therapies targeting COX-2 and CTLA-4 in HGSOC. Full article
(This article belongs to the Special Issue Advances in the Treatment of Ovarian Cancer)
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15 pages, 1859 KiB  
Article
Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission
by Beryl L. Manning-Geist, Sacha Gnjatic, Carol Aghajanian, Jason Konner, Sarah H. Kim, Debra Sarasohn, Krysten Soldan, William P. Tew, Nicholas J. Sarlis, Dmitriy Zamarin, Sara Kravetz, Ilaria Laface, Teresa Rasalan-Ho, Jingjing Qi, Phillip Wong, Paul J. Sabbatini and Roisin E. O’Cearbhaill
Cancers 2023, 15(5), 1458; https://doi.org/10.3390/cancers15051458 - 25 Feb 2023
Cited by 5 | Viewed by 3369
Abstract
We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms’ Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti–PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing [...] Read more.
We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms’ Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti–PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing ovarian cancer in second or third remission from June 2016 to July 2017. Therapy included six (every two weeks) subcutaneous inoculations of galinpepimut-S vaccine adjuvanted with Montanide, low-dose subcutaneous sargramostim at the injection site, with intravenous nivolumab over 12 weeks, and up to six additional doses until disease progression or toxicity. One-year progression-free survival (PFS) was correlated to T-cell responses and WT1-specific immunoglobulin (Ig)G levels. Eleven patients were enrolled; seven experienced a grade 1 adverse event, and one experienced a grade ≥3 adverse event considered a dose-limiting toxicity. Ten (91%) of eleven patients had T-cell responses to WT1 peptides. Seven (88%) of eight evaluable patients had IgG against WT1 antigen and full-length protein. In evaluable patients who received >2 treatments of galinpepimut-S and nivolumab, the 1-year PFS rate was 70%. Coadministration of galinpepimut-S and nivolumab demonstrated a tolerable toxicity profile and induced immune responses, as indicated by immunophenotyping and WT1-specific IgG production. Exploratory analysis for efficacy yielded a promising 1-year PFS rate. Full article
(This article belongs to the Special Issue Advances in the Treatment of Ovarian Cancer)
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13 pages, 1431 KiB  
Article
Investigating the Impact of Ultra-Radical Surgery on Survival in Advanced Ovarian Cancer Using Population-Based Data in a Multicentre UK Study
by Carole Cummins, Satyam Kumar, Joanna Long, Janos Balega, Tim Broadhead, Timothy Duncan, Richard J. Edmondson, Christina Fotopoulou, Rosalind M. Glasspool, Desiree Kolomainen, Simon Leeson, Ranjit Manchanda, Jo Morrison, Raj Naik, John A. Tidy, Nick Wood and Sudha Sundar
Cancers 2022, 14(18), 4362; https://doi.org/10.3390/cancers14184362 - 7 Sep 2022
Cited by 8 | Viewed by 3188
Abstract
We investigated URS and impact on survival in whole patient cohorts with AOC treated within gynaecological cancer centres that participated in the previously presented SOCQER 2 study. National cancer registry datasets were used to identify FIGO Stage 3,4 and unknown stage patients from [...] Read more.
We investigated URS and impact on survival in whole patient cohorts with AOC treated within gynaecological cancer centres that participated in the previously presented SOCQER 2 study. National cancer registry datasets were used to identify FIGO Stage 3,4 and unknown stage patients from 11 cancer centres that had previously participated in the SOCQER2 study. Patient outcomes’ association with surgical ethos were evaluated using logistic regression and Cox proportional hazards. Centres were classified into three groups based on their surgical complexity scores (SCS); those practicing mainly low complexity, (5/11 centres with >70% low SCS procedures, 759 patients), mainly intermediate (3/11, 35–50% low SCS, 356 patients), or mainly high complexity surgery (3/11, >35% high SCS, 356 patients). Surgery rates were 43.2% vs. 58.4% vs. 60.9%. across mainly low, intermediate and high SCS centres, respectively, p < 0.001. Combined surgery and chemotherapy rates were 39.2% vs. 51.8% vs. 38.3% p < 0.000 across mainly low, intermediate and high complexity groups, respectively. Median survival was 23.1 (95% CI 19.0 to 27.2) vs. 22.0 (95% CI 17.6 to 26.3) vs. 17.9 months (95% CI 15.7 to 20.1), p = 0.043 in mainly high SCS, intermediate, and low SCS centres, respectively. In an age and deprivation adjusted model, compared to patients in the high SCS centres, patients in the low SCS group had an HR of 1.21 (95% CI 1.03 to 1.40) for death. Mainly high/intermediate SCS centres have significantly higher surgery rates and better survival at a population level. Centres that practice mainly low complexity surgery should change practice. This study provides support for the utilization of URS for patients with advanced OC. Full article
(This article belongs to the Special Issue Advances in the Treatment of Ovarian Cancer)
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