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Special Issue "Ovarian Cancer: Prevention and Treatment"

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A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Women's Health".

Deadline for manuscript submissions: 31 August 2023 | Viewed by 8717

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Special Issue Editors

Dr. Stergios Boussios

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Guest Editor

1. Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, King's College London, London SE1 9RT, UK
2. Medway NHS Foundation Trust, Windmill Road, Gillingham, Kent ME7 5NY, UK
3. Kent Medway Medical School, University of Kent, CT2 7LX, Canterbury, Kent, UK
4. AELIA Organization, 9(th)Km Thessaloniki-Thermi, 57001 Thessaloniki, Greece
Interests: ovarian cancer; cervical cancer; carcinoma of unknown primary; prostate cancer, renal cancer, colorectal cancer; cancer in pregnancy
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Prof. Dr. Matin Sheriff

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Guest Editor

Medway NHS Foundation Trust, Windmill Road, Gillingham, Kent ME7 5NY, UK
Interests: prostate cancer; urology oncology; minimally invasive surgery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ovarian cancer is composed of three histological subtypes: epithelial (90%), germ cell (5%), and sex cord stromal cell (5%). Epithelial ovarian cancer (EOC) is deadly, claiming more women than all other gynecological malignancies combined, due to lack of effective early detection strategies. The majority of newly diagnosed EOC patients are treated with radical surgery, followed by adjuvant platinum-based chemotherapy. Most patients experience disease relapse within the first 5 years, despite aggressive treatment at diagnosis.

Screening efforts and genetic testing is strongly recommended. The analysis should be able to detect damaging variants in all genes associated with EOC susceptibility and next-generation sequencing (NGS) technologies have rapidly evolved. Breast cancer genes 1 and 2 (BRCA1/2) germline mutations are the most significant molecular aberrations in EOC with established prognostic and predictive value. Cells with mutations in BRCA1/2 genes have an impaired double-strand DNA breaks (DSBs). Apart from BRCA1/2, several other suppressor genes and oncogenes have been associated with hereditary EOC (i.e., TP53, BARD1, CHEK2, RAD51, and PALB2).

There is mature evidence that poly (ADP-ribose) polymerase (PARP) inhibitors exploit homologous recombination (HR) deficiency, especially in patients with BRCA1/2 mutations. Moreover, novel combinations of PARP inhibitors with other anticancer therapies are challenging; the first evaluated combination was with antiangiogenic agents. In addition, encouraging preliminary results support the combination of PARP and immune checkpoint inhibitors. Other biologic agents that have been combined with PARP inhibitors are the anti-CTLA4 monoclonal antibodies, and the mTOR-, AKT-, PI3K-, MEK1/2-, and WEE1 inhibitors. Finally, combination with chemotherapy has been recommended with the rationale of disrupting base excision repair via PARP inhibition.

The forthcoming special issue focuses on several key elements that are essential for an understanding of this heterogeneous group of malignancies. The manuscripts should be focused but are not only limited to:

Risk factors for ovarian cancer
EOC risk assessment in the era of next-generation sequencing
PARP inhibitors in EOC
PARP inhibitors in combination with other therapies
Immunotherapy in EOC
Endometriosis-associated EOC
Diagnosis and treatment of non-epithelial ovarian cancers

Dr. Stergios Boussios
Prof. Dr. Matin Sheriff
Guest Editors

Manuscript Submission Information

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Keywords

ovarian cancer
germaline mutations
somatic mutations
DNA repair pathways
cell cycle related genes
PARP inhibitors
combined therapies
precision treatment

Published Papers (5 papers)

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Research

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Open AccessArticle

Clinical Performance of a Multivariate Index Assay in Detecting Early-Stage Ovarian Cancer in Filipino Women

and

Ourlad Alzeus G. Tantengco

Int. J. Environ. Res. Public Health 2022, 19(16), 9896; https://doi.org/10.3390/ijerph19169896 - 11 Aug 2022

Cited by 1 | Viewed by 1408

Abstract

This study evaluated the clinical performance and overall utility of a multivariate index assay in detecting early-stage ovarian cancer in a Filipino population. This is a prospective cohort study among Filipino women undergoing assessment for an ovarian mass in a tertiary center. Patients diagnosed with early-stage ovarian cancer and who underwent a physical examination before level III specialist ultrasonographic and Doppler evaluation, multivariate index assay (MIA2G), and surgery for an adnexal mass were included in this study. Ovarian tumors were classified as high-risk for malignancy based on the IOTA-LR2 score. The ovarian imaging and biomarker results were correlated with the reference standard: surgico-pathologic findings. The MIA2G exhibited the best overall performance among individual classifiers with a sensitivity of 91.7% and NPV of 84.7%, with a concomitant higher sensitivity in early-stage disease, whether as an individual classifier (93.5%) or in serial combination with ultrasound (85.5%). The performance of biomarkers (specificity, positive predictive values, and AUROC) such as MIA2G and CA-125 significantly improved when combined with an ultrasound risk scoring approach (p < 0.01). MIA2G showed a higher sensitivity for detecting lesions among EOC and late-stage ovarian cancers than otherwise. The application of biomarkers for evaluating ovarian masses in our local setting is secondary to ultrasound but adopting multivariate index assays rather than CA-125 would increase the detection of early-stage ovarian cancers regardless of menopausal status. This is most relevant in areas where level III sonographers or gynecologic oncologists are limited and preoperative referrals to these specialists can improve the survival of our patients. Full article

(This article belongs to the Special Issue Ovarian Cancer: Prevention and Treatment)

Review

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Open AccessReview

Hereditary Ovarian Cancer: Towards a Cost-Effective Prevention Strategy

Kathrine Sofia Rallis

and

Stergios Boussios

Int. J. Environ. Res. Public Health 2022, 19(19), 12057; https://doi.org/10.3390/ijerph191912057 - 23 Sep 2022

Cited by 1 | Viewed by 1148

Abstract

Ovarian cancer (OC) is the most lethal gynaecological malignancy. The search for a widely affordable and accessible screening strategy to reduce mortality from OC is still ongoing. This coupled with the late-stage presentation and poor prognosis harbours significant health-economic implications. OC is also the most heritable of all cancers, with an estimated 25% of cases having a hereditary predisposition. Advancements in technology have detected multiple mutations, with the majority affecting the BRCA1 and/or BRCA2 genes. Women with BRCA mutations are at a significantly increased lifetime risk of developing OC, often presenting with a high-grade serous pathology, which is associated with higher mortality due to its aggressive characteristic. Therefore, a targeted, cost-effective approach to prevention is paramount to improve clinical outcomes and mortality. Current guidelines offer multiple preventive strategies for individuals with hereditary OC (HOC), including genetic counselling to identify the high-risk women and risk-reducing interventions (RRI), such as surgical management or chemoprophylaxis through contraceptive medications. Evidence for sporadic OC is abundant as compared to the existing dearth in the hereditary subgroup. Hence, our review article narrates an overview of HOC and explores the RRI developed over the years. It attempts to compare the cost effectiveness of these strategies with women of the general population in order to answer the crucial question: what is the most prudent clinically and economically effective strategy for prevention amongst high-risk women? Full article

(This article belongs to the Special Issue Ovarian Cancer: Prevention and Treatment)

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Open AccessFeature PaperReview

Recent Insights into PARP and Immuno-Checkpoint Inhibitors in Epithelial Ovarian Cancer

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Int. J. Environ. Res. Public Health 2022, 19(14), 8577; https://doi.org/10.3390/ijerph19148577 - 14 Jul 2022

Cited by 11 | Viewed by 2002

Abstract

Ovarian cancer is one of the most common gynecologic cancers and has the highest mortality rate of any other cancer of the female reproductive system. Epithelial ovarian cancer (EOC) accounts for approximately 90% of all ovarian malignancies. The standard therapeutic strategy includes cytoreductive surgery accompanied by pre- or postoperative platinum-based chemotherapy. Nevertheless, up to 80% of the patients relapse within the following 12–18 months from the completion of the treatment and then receive first-line chemotherapy depending on platinum sensitivity. Mutations in BRCA1/2 genes are the most significant molecular aberrations in EOC and serve as prognostic and predictive biomarkers. Poly ADP-ribose polymerase (PARP) inhibitors exploit defects in the DNA repair pathway through synthetic lethality. They have also been shown to trap PARP1 and PARP2 on DNA, leading to PARP-DNA complexes. Olaparib, rucaparib, and niraparib have all obtained Food and Drug Administration (FDA) and/or the European Medicine Agency (EMA) approval for the treatment of EOC in different settings. Immune checkpoint inhibitors (ICI) have improved the survival of several cancers and are under evaluation in EOC. However, despite the success of immunotherapy in other malignancies, the use of antibodies inhibiting the immune checkpoint programmed cell death (PD-1) or its ligand (PD-L1) obtained modest results in EOC so far, with median response rates of up to 10%. As such, ICI have not yet been approved for the treatment of EOC. We herein provided a comprehensive insight into the most recent progress in synthetic lethality PARP inhibitors, along with the mechanisms of resistance. We also summarised data regarding the role of immune checkpoint inhibitors, the use of vaccination therapy, and adoptive immunotherapy in treating epithelial ovarian cancer. Full article

(This article belongs to the Special Issue Ovarian Cancer: Prevention and Treatment)

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Open AccessReview

Epithelial Ovarian Cancer: Providing Evidence of Predisposition Genes

and

Int. J. Environ. Res. Public Health 2022, 19(13), 8113; https://doi.org/10.3390/ijerph19138113 - 01 Jul 2022

Cited by 9 | Viewed by 1518

Abstract

Epithelial ovarian cancer (EOC) is one of the cancers most influenced by hereditary factors. A fourth to a fifth of unselected EOC patients carry pathogenic variants (PVs) in a number of genes, the majority of which encode for proteins involved in DNA mismatch repair (MMR) pathways. PVs in BRCA1 and BRCA2 genes are responsible for a substantial fraction of hereditary EOC. In addition, PV genes involved in the MMR pathway account for 10–15% of hereditary EOC. The identification of women with homologous recombination (HR)-deficient EOCs has significant clinical implications, concerning chemotherapy regimen planning and development as well as the use of targeted therapies such as poly(ADP-ribose) polymerase (PARP) inhibitors. With several genes involved, the complexity of genetic testing increases. In this context, next-generation sequencing (NGS) allows testing for multiple genes simultaneously with a rapid turnaround time. In this review, we discuss the EOC risk assessment in the era of NGS. Full article

(This article belongs to the Special Issue Ovarian Cancer: Prevention and Treatment)

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Open AccessReview

Non-Epithelial Ovarian Cancers: How Much Do We Really Know?

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Int. J. Environ. Res. Public Health 2022, 19(3), 1106; https://doi.org/10.3390/ijerph19031106 - 19 Jan 2022

Cited by 16 | Viewed by 1737

Abstract

Non-epithelial ovarian cancers (NEOC) are a group of uncommon malignancies that mainly includes germ cell tumours (GCT), sex cord-stromal tumours (SCST), and some extremely rare tumours, such as small cell carcinomas and sarcomas. Each of these classifications encompasses multiple histologic subtypes. The aetiology and molecular origins of each sub-group of NEOC require further investigation, and our understanding on the genetic changes should be optimised. In this article, we provide an update on the clinical presentation, pathology, genetics, treatment and survival of the main histological subtypes of the GCT and the SCST, as well as of ovarian small cell carcinomas. We also discuss miRNA expression profiles of NEOC and report the currently active clinical trials that include NEOC. Full article

(This article belongs to the Special Issue Ovarian Cancer: Prevention and Treatment)

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