Ovarian Cancer in the Age of Precision Medicine

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Gynecologic Oncology".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 17679

Special Issue Editor


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Guest Editor
Ovarian Cancer Canada, Toronto, ON M5A 1E3, Canada
Interests: ovarian cancer; prevention; genetics; molecular pathology; precision oncology; patient engagement

Special Issue Information

Dear Colleagues,

Ovarian cancer remains the most fatal gynecologic malignancy, with no effective screening modalities or diagnostic tests. While recent treatment advances are enabling a subset of people diagnosed with ovarian cancer to live longer with a better quality of life, few options exist for many patients and long-term survival outcomes have not changed in 50 years. This Special Issue will focus on the progress, challenges, and promise of omics to enable precision medicine for individuals with all types of ovarian cancer and how advances in precision medicine along the entire care continuum (prevention, diagnosis, treatment, survivorship) are needed to improve patient outcomes. The important role of the patient voice in shaping precision medicine strategies—in addition to equitable access to advances for all individuals with or at risk for ovarian cancer—will also be included.

In this Special Issue, original research articles, commentaries, and reviews are welcome. Research areas may include (but are not limited to) the following:

  • New samples, technologies, and/or approaches for early detection, most notably for high-grade serous ovarian/tubal/peritoneal cancer;
  • Targeted prevention strategies based on lifetime risk of ovarian cancer;
  • Novel precision treatments for less common types of ovarian cancer;
  • Understanding and overcoming resistance to targeted treatments;
  • Using omics to increase the efficacy of immune-based treatments in ovarian cancer;
  • Patient engagement in basic, preclinical, and clinical research investigating precision medicine strategies;
  • Novel approaches for personalized survivorship.

I look forward to receiving your contributions. 

Dr. Alicia A. Tone
Guest Editor

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Keywords

  • ovarian cancer
  • omics
  • prevention
  • diagnosis
  • treatment
  • survivorship
  • equity
  • patient engagement
 

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Published Papers (9 papers)

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Research

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9 pages, 1049 KiB  
Article
Assessment of the American College of Surgeons Surgical Risk Calculator (ACS-SRC) for Prediction of Early Postoperative Complications in Patients Undergoing Cytoreductive Surgery for Ovarian Peritoneal Carcinomatosis
by Cedric Kabeya, Charif Khaled, Laura Polastro, Michel Moreau, Dario Bucella, Maxime Fastrez and Gabriel Liberale
Curr. Oncol. 2024, 31(12), 7863-7871; https://doi.org/10.3390/curroncol31120579 - 7 Dec 2024
Viewed by 721
Abstract
Ovarian cancer (OC) is diagnosed at a locally advanced stage in two-thirds of cases. The first line of treatment consists of cytoreductive surgery (CRS) combined with neoadjuvant and/or adjuvant chemotherapy. However, CRS can be associated with high rates of postoperative complications (POCs), and [...] Read more.
Ovarian cancer (OC) is diagnosed at a locally advanced stage in two-thirds of cases. The first line of treatment consists of cytoreductive surgery (CRS) combined with neoadjuvant and/or adjuvant chemotherapy. However, CRS can be associated with high rates of postoperative complications (POCs), and detection of fragile patients at high risk of POCs is important. The American College of Surgeons Surgical Risk Calculator (ACS-SRC) provides a predictive model for early POCs (30 days) for any given surgical procedure. This study aimed to evaluate the performance of the ACS-SRC in predicting the occurrence of early POCs for patients undergoing CRS for OC. This was a retrospective study that included patients undergoing CRS for advanced OC between January 2010 and December 2022. Early POCs were reviewed, and the rate of POCs was compared with those predicted by the ACS-SRC to evaluate its accuracy (i.e., discrimination and calibration). A total of 218 patients were included, 112 of whom underwent extensive surgery/resection. A total of 94 complications were recorded. This cohort demonstrated correct calibration of the ACS-SRC for the prediction of surgical site infection, readmission, and the need for nursing care post-discharge (NCPD; transfer to revalidation center or need for nursing care at home). Using both the discrimination and calibration methods, the score only predicted NCPD. In this study, the ACS-SRC was shown to be of little value for patients undergoing cytoreductive surgery for ovarian peritoneal carcinomatosis, as it only accurately predicted NCPD. Full article
(This article belongs to the Special Issue Ovarian Cancer in the Age of Precision Medicine)
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23 pages, 2971 KiB  
Article
Advancing Research Alongside Patient Partners: Next-Generation Best Practices for Effective Collaboration in Health Research
by Ally C. Farrell, Jessica A. Lawson, Ovarian Cancer Canada’s Patient Partners in Research Team, Alison Ross and Alicia A. Tone
Curr. Oncol. 2024, 31(11), 6956-6978; https://doi.org/10.3390/curroncol31110513 - 7 Nov 2024
Viewed by 1733
Abstract
Ovarian Cancer Canada’s Patient Partners in Research (PPiR) is a national volunteer-based program that trains and connects individuals with lived ovarian cancer (OC) experience to diverse research opportunities, to maximize the clinical relevance and real-life impact of OC research in Canada. A steadily [...] Read more.
Ovarian Cancer Canada’s Patient Partners in Research (PPiR) is a national volunteer-based program that trains and connects individuals with lived ovarian cancer (OC) experience to diverse research opportunities, to maximize the clinical relevance and real-life impact of OC research in Canada. A steadily increasing demand for patient partners to be involved as research team members and decision-makers led us to co-develop with the PPiR team a series of “best practices” for researcher–patient partnerships. This framework formalizes our evolving approach to patient engagement and begins to address challenges that can arise in research settings focused on less commonly diagnosed yet significant and fatal diseases such as OC: (1) Start early. (2) Foster collaboration among the entire research team. (3) Establish expectations and communicate regularly. (4) Report impact of patient partner contributions. (5) Ensure adequate resources. While there are ongoing challenges associated with patient engagement that need to be addressed, data collected from an anonymous survey of Canadian OC researchers show a marked improvement in perceived benefits of patient engagement over time and validate the best practices presented herein. Developed in the context of OC research, these best practices can be adapted to a variety of health research settings with similar challenges. Full article
(This article belongs to the Special Issue Ovarian Cancer in the Age of Precision Medicine)
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14 pages, 1584 KiB  
Article
Ovarian Mesonephric-like Adenocarcinoma: Its Prevalence in a Japanese High-Volume Cancer Center and a Literature Review on Therapeutic Targets
by Ayako Ogawa, Hiroshi Yoshida, Saria Kawano, Nao Kikkawa, Mayumi Kobayashi-Kato, Yasuhito Tanase, Masaya Uno and Mitsuya Ishikawa
Curr. Oncol. 2024, 31(9), 5107-5120; https://doi.org/10.3390/curroncol31090378 - 30 Aug 2024
Viewed by 1654
Abstract
Background: Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review the existing literature, and elucidate its clinicopathological characteristics, including the potential therapeutic targets. Methods: We retrospectively [...] Read more.
Background: Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review the existing literature, and elucidate its clinicopathological characteristics, including the potential therapeutic targets. Methods: We retrospectively reviewed the pathological diagnoses of 501 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLAs. Results: Among the 501 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52–76 years old, and the initial FIGO stages were IC1 (two cases) and IIIB (one case). All the cases exhibited HRP, pMMR, PD-L1 negativity (CPS < 1), and low HER2 expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. The MLAs frequently exhibited KRAS mutations (90%, 38/42), with a recurrence rate of 39% (26/67). Conclusion: MLAs accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. The literature also reported a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA. Full article
(This article belongs to the Special Issue Ovarian Cancer in the Age of Precision Medicine)
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12 pages, 992 KiB  
Article
Real-World Safety of Niraparib for Maintenance Treatment of Ovarian Cancer in Canada
by Qi Guan, Suriya J. Aktar, Reka E. Pataky, Mariet Mathew Stephen, Maud Marques, Karen Gambaro, Kahina Rachedi, Katharina Forster, Samara Strub, David Stock, Louis de Léséleuc, Winson Y. Cheung, Stuart Peacock, Christie Farrer, Scott Gavura, Mina Tadrous, Robert C. Grant and Kelvin K. W. Chan
Curr. Oncol. 2024, 31(6), 3591-3602; https://doi.org/10.3390/curroncol31060264 - 19 Jun 2024
Viewed by 1825
Abstract
Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug’s safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that [...] Read more.
Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug’s safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11–16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3–15.4%), neutropenia was 7.1% (95% CI, 4.6–10.4%), and anemia was 11.3% (95% CI, 8.0–15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians. Full article
(This article belongs to the Special Issue Ovarian Cancer in the Age of Precision Medicine)
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23 pages, 3577 KiB  
Article
Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens
by Leslie Hesnard, Catherine Thériault, Maxime Cahuzac, Chantal Durette, Krystel Vincent, Marie-Pierre Hardy, Joël Lanoix, Gabriel Ouellet Lavallée, Juliette Humeau, Pierre Thibault and Claude Perreault
Curr. Oncol. 2024, 31(6), 3099-3121; https://doi.org/10.3390/curroncol31060236 - 30 May 2024
Viewed by 1458
Abstract
Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. [...] Read more.
Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy. Full article
(This article belongs to the Special Issue Ovarian Cancer in the Age of Precision Medicine)
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10 pages, 1507 KiB  
Article
The Development and Testing of a Patient Decision Aid for Individuals with Homologous Recombinant Proficient Ovarian Cancer Who Are Considering Niraparib Maintenance Therapy
by Laura Hopkins, Mark Carey, Linda Brown, Sabryna McCrea, Mark Milne, Dawne Tokaryk and Dawn Stacey
Curr. Oncol. 2024, 31(3), 1416-1425; https://doi.org/10.3390/curroncol31030107 - 8 Mar 2024
Viewed by 1880
Abstract
New treatments for ovarian cancer are available that require trade-offs between progression-free survival and quality of life. The aim of this study was to develop a decision aid for patients with homologous recombinant proficient (HRP) tumors, as the benefit–harm ratio of niraparib needs [...] Read more.
New treatments for ovarian cancer are available that require trade-offs between progression-free survival and quality of life. The aim of this study was to develop a decision aid for patients with homologous recombinant proficient (HRP) tumors, as the benefit–harm ratio of niraparib needs consideration. This decision aid was created with a systematic and iterative development process based on the Ottawa Decision Support Framework. The decision aid was user-tested for acceptability, usability, and comprehensibility using a survey completed by a sample of patients with ovarian cancer and oncologists. This decision aid follows the International Patient Decision Aids Standards (IPDAS) criteria in its development. User-test respondents (n = 13 patients; 13 physicians) reported that the decision aid used language that was easy to follow (69% patients; 85% physicians), was an appropriate length (69% patients; 62% physicians) and provided the right amount of information (54% patients; 54% physicians). Most respondents (92% patients; 62% physicians) would recommend this decision aid for HRP patients considering niraparib. This is the first decision aid for patients with HRP ovarian cancers who are considering niraparib maintenance therapy. It is available on-line and is being further evaluated in a pragmatic clinical trial in Saskatchewan. Full article
(This article belongs to the Special Issue Ovarian Cancer in the Age of Precision Medicine)
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Review

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16 pages, 689 KiB  
Review
Challenges in Implementing Comprehensive Precision Medicine Screening for Ovarian Cancer
by Laura R. Moffitt, Nazanin Karimnia, Amy L. Wilson, Andrew N. Stephens, Gwo-Yaw Ho and Maree Bilandzic
Curr. Oncol. 2024, 31(12), 8023-8038; https://doi.org/10.3390/curroncol31120592 - 18 Dec 2024
Viewed by 668
Abstract
Precision medicine has revolutionised targeted cancer treatments; however, its implementation in ovarian cancer remains challenging. Diverse tumour biology and extensive heterogeneity in ovarian cancer can limit the translatability of genetic profiling and contribute to a lack of biomarkers of treatment response. This review [...] Read more.
Precision medicine has revolutionised targeted cancer treatments; however, its implementation in ovarian cancer remains challenging. Diverse tumour biology and extensive heterogeneity in ovarian cancer can limit the translatability of genetic profiling and contribute to a lack of biomarkers of treatment response. This review addresses the barriers in precision medicine for ovarian cancer, including obtaining adequate and representative tissue samples for analysis, developing functional and standardised screening methods, and navigating data infrastructure and management. Ethical concerns related to patient consent, data privacy and health equity are also explored. We highlight the socio-economic complexities for precision medicine and propose strategies to overcome these challenges with an emphasis on accessibility and education amongst patients and health professionals and the development of regulatory frameworks to support clinical integration. Interdisciplinary collaboration is essential to drive progress in precision medicine to improve disease management and ovarian cancer patient outcomes. Full article
(This article belongs to the Special Issue Ovarian Cancer in the Age of Precision Medicine)
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19 pages, 1720 KiB  
Review
The Complex Tumor Microenvironment in Ovarian Cancer: Therapeutic Challenges and Opportunities
by Bianca Garlisi, Sylvia Lauks, Caroline Aitken, Leslie M. Ogilvie, Cielle Lockington, Duncan Petrik, Jan Soeren Eichhorn and Jim Petrik
Curr. Oncol. 2024, 31(7), 3826-3844; https://doi.org/10.3390/curroncol31070283 - 1 Jul 2024
Cited by 5 | Viewed by 3437
Abstract
The tumor microenvironment (TME) in ovarian cancer (OC) has much greater complexity than previously understood. In response to aggressive pro-angiogenic stimulus, blood vessels form rapidly and are dysfunctional, resulting in poor perfusion, tissue hypoxia, and leakiness, which leads to increased interstitial fluid pressure [...] Read more.
The tumor microenvironment (TME) in ovarian cancer (OC) has much greater complexity than previously understood. In response to aggressive pro-angiogenic stimulus, blood vessels form rapidly and are dysfunctional, resulting in poor perfusion, tissue hypoxia, and leakiness, which leads to increased interstitial fluid pressure (IFP). Decreased perfusion and high IFP significantly inhibit the uptake of therapies into the tumor. Within the TME, there are numerous inhibitor cells, such as myeloid-derived suppressor cells (MDSCs), tumor association macrophages (TAMs), regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs) that secrete high numbers of immunosuppressive cytokines. This immunosuppressive environment is thought to contribute to the lack of success of immunotherapies such as immune checkpoint inhibitor (ICI) treatment. This review discusses the components of the TME in OC, how these characteristics impede therapeutic efficacy, and some strategies to alleviate this inhibition. Full article
(This article belongs to the Special Issue Ovarian Cancer in the Age of Precision Medicine)
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16 pages, 1586 KiB  
Review
Ovarian Cancer: From Precursor Lesion Identification to Population-Based Prevention Programs
by Ramlogan Sowamber, Alexandra Lukey, David Huntsman and Gillian Hanley
Curr. Oncol. 2023, 30(12), 10179-10194; https://doi.org/10.3390/curroncol30120741 - 29 Nov 2023
Cited by 7 | Viewed by 2765
Abstract
Epithelial ovarian cancer (EOC) is a heterogeneous group of malignancies, including high-grade serous ovarian cancer (HGSC). HGSC is often diagnosed at advanced stages and is linked to TP53 variants. While BRCA variants elevate risk, most HGSC cases occur in individuals without known genetic [...] Read more.
Epithelial ovarian cancer (EOC) is a heterogeneous group of malignancies, including high-grade serous ovarian cancer (HGSC). HGSC is often diagnosed at advanced stages and is linked to TP53 variants. While BRCA variants elevate risk, most HGSC cases occur in individuals without known genetic variants, necessitating prevention strategies for people without known high-risk genetic variants. Effective prevention programs are also needed due to the lack of traditional screening options. An emerging primary prevention strategy is opportunistic salpingectomy, which involves removing fallopian tubes during another planned pelvic surgery. Opportunistic salpingectomy offers a safe and cost-effective preventative option that is gaining global adoption. With the publication of the first cohort study of patients who underwent salpingectomy, specifically for cancer prevention, attention has turned to broadening opportunities for salpingectomy in addition to more targeted approaches. Prevention opportunities are promising with increasing adoption of salpingectomy and the increased understanding of the etiology of the distinct histotypes of ovarian cancer. Yet, further research on targeted risk-reducing salpingectomy with thoughtful consideration of equity is necessary to reduce death and suffering from ovarian cancer. Full article
(This article belongs to the Special Issue Ovarian Cancer in the Age of Precision Medicine)
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